major his to compatibility complex

8/2/2019 Major His to Compatibility Complex

1/12

Major histocompatibility complexFrom Wikipedia, the free encyclopedia

Majorhistocompatibilitycomplex (MHC) is a cell surface molecule encoded by a largegene familyin

allvertebrates. MHC molecules mediate interactions ofleukocytes, also calledwhite blood cells(WBCs), whichareimmune cells, with other leukocytes or body cells. MHC determines compatibility of donors fororgan

transplantas well as one's susceptibility to anautoimmune diseaseviacrossreactingimmunization. In humans,

MHC is also calledhuman leukocyte antigen(HLA).

Proteinmoleculeseither of the host's ownphenotypeor of other biologic entitiesare continually synthesized

and degraded in acell. Occurring on the cell surface, each MHC molecule displays a molecular fraction,

calledepitope, of a protein, somewhat like a hot dog (epitope) within a bun (MHC).[1]

The presented antigen

can be either selfor nonself. On the cell membrane, the MHC population in its entirety is like a meter indicating

the balance of proteins within the cell.

The MHC gene family is divided into three subgroupsclass I, class II, and class III. Diversity of antigen

presentation, mediated by MHC classes I and II, is attained in multiple ways: (1) the MHC's genetic encoding

ispolygenic, (2) MHC genes are highly polymorphic and have manyvariants, (3) several MHC genes are

expressed from both inheritedalleles.

Contents

[hide]

1 MHC in animal immunity

2 MHC genes

3 MHC proteins

o 3.1 Class I

o 3.2 Class II

o 3.3 Class III

4 Antigen processing and presentation

5 T lymphocyte recognition restrictions

6 MHC in sexual mate selection

7 MHC evolutionary diversity

8 MHC in transplant rejection

9 HLA biology

10 See also

11 References
http://en.wikipedia.org/wiki/Histocompatibilityhttp://en.wikipedia.org/wiki/Histocompatibilityhttp://en.wikipedia.org/wiki/Histocompatibilityhttp://en.wikipedia.org/wiki/Gene_familyhttp://en.wikipedia.org/wiki/Gene_familyhttp://en.wikipedia.org/wiki/Gene_familyhttp://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/wiki/White_blood_cellshttp://en.wikipedia.org/wiki/White_blood_cellshttp://en.wikipedia.org/wiki/White_blood_cellshttp://en.wikipedia.org/wiki/Immune_cellshttp://en.wikipedia.org/wiki/Immune_cellshttp://en.wikipedia.org/wiki/Immune_cellshttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Autoimmune_diseasehttp://en.wikipedia.org/wiki/Autoimmune_diseasehttp://en.wikipedia.org/wiki/Autoimmune_diseasehttp://en.wikipedia.org/w/index.php?title=Crossreaction&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Crossreaction&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Crossreaction&action=edit&redlink=1http://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Epitopehttp://en.wikipedia.org/wiki/Epitopehttp://en.wikipedia.org/wiki/Epitopehttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-0http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-0http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-0http://en.wikipedia.org/wiki/Polygenichttp://en.wikipedia.org/wiki/Polygenichttp://en.wikipedia.org/wiki/Polygenichttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Major_histocompatibility_complexhttp://en.wikipedia.org/wiki/Major_histocompatibility_complexhttp://en.wikipedia.org/wiki/Major_histocompatibility_complexhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_animal_immunityhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_animal_immunityhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_geneshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_geneshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_proteinshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_proteinshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_Ihttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_Ihttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_IIhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_IIhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_IIIhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_IIIhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Antigen_processing_and_presentationhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Antigen_processing_and_presentationhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#T_lymphocyte_recognition_restrictionshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#T_lymphocyte_recognition_restrictionshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_sexual_mate_selectionhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_sexual_mate_selectionhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_evolutionary_diversityhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_evolutionary_diversityhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_transplant_rejectionhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_transplant_rejectionhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#HLA_biologyhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#HLA_biologyhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#See_alsohttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#See_alsohttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Referenceshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Referenceshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Referenceshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#See_alsohttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#HLA_biologyhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_transplant_rejectionhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_evolutionary_diversityhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_sexual_mate_selectionhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#T_lymphocyte_recognition_restrictionshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Antigen_processing_and_presentationhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_IIIhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_IIhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#Class_Ihttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_proteinshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_geneshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#MHC_in_animal_immunityhttp://en.wikipedia.org/wiki/Major_histocompatibility_complexhttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Alleleshttp://en.wikipedia.org/wiki/Polygenichttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-0http://en.wikipedia.org/wiki/Epitopehttp://en.wikipedia.org/wiki/Cell_(biology)http://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Proteinhttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/w/index.php?title=Crossreaction&action=edit&redlink=1http://en.wikipedia.org/wiki/Autoimmune_diseasehttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Immune_cellshttp://en.wikipedia.org/wiki/White_blood_cellshttp://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/wiki/Gene_familyhttp://en.wikipedia.org/wiki/Histocompatibility


2/12

12 External links

[edit]MHC in animal immunity

Of the three MHC classes identified, human focus commonly goes to class I and class II. MHC class II

mediates immunizationspecific immunityto an antigen. MHC class I thereafter mediates destruction of host

cells displaying that antigen.

Some matureleukocytesof the lineagelymphocyteresiding in peripheral lymphoid tissues such aslymphoid

folliclesandlymph nodesbear receptors that ligate MHC.T cells, which are lymphocytes ofspecific immunity,

as well asnatural killer cells(NK cells), which are lymphocytes that act innately, interact with MHC. When MHC

class I expression is low altogethersuggesting abnormal cell functionNK cells promptprogrammed cell

deathof the cell. (B cellsthe other lymphocyte mediating specific immunitysecrete antibody molecules but

do not ligate MHC.)

MHC class II can be conditionally expressed by all cell types, but normally occurs only on professionalantigen-

presenting cells(APCs):macrophages,B cells, and especiallydendritic cells(DCs). An APC uptakes an

antigen, performsantigen processing, and returns a molecular fractionthe epitopeto the APC's surface

within an MHC class II molecule forantigen presentation. TheCD4receptors borne by naivehelper T

cellsligate MHC class II while the epitopewithin the MHC class II moleculeimprints theT cell

receptor(TCR) of the naive helper T cell, memorizing that epitope. The APC meanwhile

secretescytokinesprompting differentiation of the helper T cell (Th) from naivephenotype(Th0) into a

particular effector phenotype, either type 1 (Th1), type 2 (Th2), type 17 (Th17), or regulatory phenotype (Treg),

as so far identified. Thus MHC class II mediates immunization toor, if helping prime Treg, mediatesimmune

toleranceofan antigen.

MHC class I occurs on allnucleatedcellsin essence all cells butred blood cells. MHC class I presents

epitopes tocytotoxic T cells, also called killer T cells, which express theCD8molecule. When its CD8 docks to

MHC class I, if its TCR recognizes its matching epitope, the killer T cell induces the cell'sapoptosis. Thus MHC

class I helps mediatecellular immunity. (B cells express MHC class II to present antigen to Th0, but when itsB

cell receptoris ligated by its own matching epitopean interaction not mediated by MHCthe activated B cell

secretes solubleimmunoglobulins:antibodymolecules mediatinghumoral immunity.)

[edit]MHC genes

MHC gene families are found in allvertebrates, though they vary widely,chickenshaving among the smallest

known MHC regions (19 genes). Inhumansthe MHC region occurs on chromosome 6, between the

flankinggenetic markersMOG and COL11A2, and contains 140 genes spanning 3.6 megabase pairs(3.6 Mb

or 3 600 000 bits).[2]

About half have known immune functions.
http://en.wikipedia.org/wiki/Major_histocompatibility_complex#Referenceshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#External_linkshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#External_linkshttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=1http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=1http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=1http://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/wiki/Lymphocytehttp://en.wikipedia.org/wiki/Lymphocytehttp://en.wikipedia.org/wiki/Lymphoid_follicleshttp://en.wikipedia.org/wiki/Lymphoid_follicleshttp://en.wikipedia.org/wiki/Lymphoid_follicleshttp://en.wikipedia.org/wiki/Lymphoid_follicleshttp://en.wikipedia.org/wiki/Lymph_nodeshttp://en.wikipedia.org/wiki/Lymph_nodeshttp://en.wikipedia.org/wiki/T_cellshttp://en.wikipedia.org/wiki/T_cellshttp://en.wikipedia.org/wiki/T_cellshttp://en.wikipedia.org/wiki/Specific_immunityhttp://en.wikipedia.org/wiki/Specific_immunityhttp://en.wikipedia.org/wiki/Specific_immunityhttp://en.wikipedia.org/wiki/NK_cellhttp://en.wikipedia.org/wiki/NK_cellhttp://en.wikipedia.org/wiki/NK_cellhttp://en.wikipedia.org/wiki/Programmed_cell_deathhttp://en.wikipedia.org/wiki/Programmed_cell_deathhttp://en.wikipedia.org/wiki/Programmed_cell_deathhttp://en.wikipedia.org/wiki/Programmed_cell_deathhttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/Antigen-presenting_cellshttp://en.wikipedia.org/wiki/Antigen-presenting_cellshttp://en.wikipedia.org/wiki/Antigen-presenting_cellshttp://en.wikipedia.org/wiki/Antigen-presenting_cellshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/T_cell_receptorhttp://en.wikipedia.org/wiki/T_cell_receptorhttp://en.wikipedia.org/wiki/T_cell_receptorhttp://en.wikipedia.org/wiki/T_cell_receptorhttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Immune_tolerancehttp://en.wikipedia.org/wiki/Immune_tolerancehttp://en.wikipedia.org/wiki/Immune_tolerancehttp://en.wikipedia.org/wiki/Immune_tolerancehttp://en.wikipedia.org/wiki/Nucleatedhttp://en.wikipedia.org/wiki/Nucleatedhttp://en.wikipedia.org/wiki/Nucleatedhttp://en.wikipedia.org/wiki/Red_blood_cellshttp://en.wikipedia.org/wiki/Red_blood_cellshttp://en.wikipedia.org/wiki/Red_blood_cellshttp://en.wikipedia.org/wiki/Cytotoxic_T_cellshttp://en.wikipedia.org/wiki/Cytotoxic_T_cellshttp://en.wikipedia.org/wiki/Cytotoxic_T_cellshttp://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Cellular_immunityhttp://en.wikipedia.org/wiki/Cellular_immunityhttp://en.wikipedia.org/wiki/Cellular_immunityhttp://en.wikipedia.org/wiki/B_cell_receptorhttp://en.wikipedia.org/wiki/B_cell_receptorhttp://en.wikipedia.org/wiki/B_cell_receptorhttp://en.wikipedia.org/wiki/B_cell_receptorhttp://en.wikipedia.org/wiki/Immunoglobulinshttp://en.wikipedia.org/wiki/Immunoglobulinshttp://en.wikipedia.org/wiki/Immunoglobulinshttp://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/Humoral_immunityhttp://en.wikipedia.org/wiki/Humoral_immunityhttp://en.wikipedia.org/wiki/Humoral_immunityhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=2http://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/wiki/Chickenhttp://en.wikipedia.org/wiki/Chickenhttp://en.wikipedia.org/wiki/Chickenhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Genetic_markerhttp://en.wikipedia.org/wiki/Genetic_markerhttp://en.wikipedia.org/wiki/Genetic_markerhttp://en.wikipedia.org/wiki/Base_pairshttp://en.wikipedia.org/wiki/Base_pairshttp://en.wikipedia.org/wiki/Base_pairshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-MHCsc-1http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-MHCsc-1http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-MHCsc-1http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-MHCsc-1http://en.wikipedia.org/wiki/Base_pairshttp://en.wikipedia.org/wiki/Genetic_markerhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Chickenhttp://en.wikipedia.org/wiki/Vertebratehttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=2http://en.wikipedia.org/wiki/Humoral_immunityhttp://en.wikipedia.org/wiki/Antibodyhttp://en.wikipedia.org/wiki/Immunoglobulinshttp://en.wikipedia.org/wiki/B_cell_receptorhttp://en.wikipedia.org/wiki/B_cell_receptorhttp://en.wikipedia.org/wiki/Cellular_immunityhttp://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/Cytotoxic_T_cellshttp://en.wikipedia.org/wiki/Red_blood_cellshttp://en.wikipedia.org/wiki/Nucleatedhttp://en.wikipedia.org/wiki/Immune_tolerancehttp://en.wikipedia.org/wiki/Immune_tolerancehttp://en.wikipedia.org/wiki/Phenotypehttp://en.wikipedia.org/wiki/Cytokineshttp://en.wikipedia.org/wiki/T_cell_receptorhttp://en.wikipedia.org/wiki/T_cell_receptorhttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/Antigen-presenting_cellshttp://en.wikipedia.org/wiki/Antigen-presenting_cellshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/Programmed_cell_deathhttp://en.wikipedia.org/wiki/Programmed_cell_deathhttp://en.wikipedia.org/wiki/NK_cellhttp://en.wikipedia.org/wiki/Specific_immunityhttp://en.wikipedia.org/wiki/T_cellshttp://en.wikipedia.org/wiki/Lymph_nodeshttp://en.wikipedia.org/wiki/Lymphoid_follicleshttp://en.wikipedia.org/wiki/Lymphoid_follicleshttp://en.wikipedia.org/wiki/Lymphocytehttp://en.wikipedia.org/wiki/Leukocyteshttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=1http://en.wikipedia.org/wiki/Major_histocompatibility_complex#External_links


3/12

The same markers in the gray short-tailedopossum(Monodelphis domestica), amarsupial, span 3.95 Mb

yielding 114 genes, 87 shared with humans.[3]

Marsupial MHCgenotypicvariation lies betweeneutherian

mammalsandbirdstaken as minimal MHC encodingbut is closer in organization to that of nonmammals,

and MHC class I genes of marsupials have amplified within the class II region, yielding a unique class I/II

region.[3]

Class III function very differently from class I and class II, but its locus occurs between the other two classes

onchromosome 6in humansand are frequently discussed together.

Class Encoding Expression

I

(1) peptide-binding proteins, which select short sequences of

amino acids forantigen presentation, as well as (2) molecules

aidingantigen-processing(such asTAPandTapasin).

One chain, called , whose ligands are

theCD8receptorborne notably

bycytotoxic T cellsand inhibitory

receptors borne byNK cells.

II

(1) peptide-binding proteins and (2) proteins assisting antigen

loading onto MHC class II's peptide-binding proteins (such

asMHC II DM,MHC II DQ,MHC II DR, andMHC II DP).

Two chains, called & , whose ligands

are theCD4receptors borne byhelper T

cells.

III

Other immune proteins, outside antigen processing and

presentation, such as components of thecomplement

cascade(e.g.,C2,C4,factor B), thecytokinesof immune signaling

(e.g.,TNF-), andheat shock proteinsbuffering cells from

stresses.

Various.

[edit]MHC proteins

MHC proteins haveimmunoglobulin-like structure.
http://en.wikipedia.org/wiki/Opossumhttp://en.wikipedia.org/wiki/Opossumhttp://en.wikipedia.org/wiki/Opossumhttp://en.wikipedia.org/wiki/Monodelphis_domesticahttp://en.wikipedia.org/wiki/Monodelphis_domesticahttp://en.wikipedia.org/wiki/Monodelphis_domesticahttp://en.wikipedia.org/wiki/Marsupialhttp://en.wikipedia.org/wiki/Marsupialhttp://en.wikipedia.org/wiki/Marsupialhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Genotypehttp://en.wikipedia.org/wiki/Genotypehttp://en.wikipedia.org/wiki/Genotypehttp://en.wikipedia.org/wiki/Eutheriahttp://en.wikipedia.org/wiki/Eutheriahttp://en.wikipedia.org/wiki/Eutheriahttp://en.wikipedia.org/wiki/Eutheriahttp://en.wikipedia.org/wiki/Birdhttp://en.wikipedia.org/wiki/Birdhttp://en.wikipedia.org/wiki/Mammalshttp://en.wikipedia.org/wiki/Mammalshttp://en.wikipedia.org/wiki/Mammalshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Chromosome_6http://en.wikipedia.org/wiki/Chromosome_6http://en.wikipedia.org/wiki/Chromosome_6http://en.wikipedia.org/wiki/MHC_class_Ihttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Tapasinhttp://en.wikipedia.org/wiki/Tapasinhttp://en.wikipedia.org/wiki/Tapasinhttp://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/Cytotoxic_T_cellshttp://en.wikipedia.org/wiki/Cytotoxic_T_cellshttp://en.wikipedia.org/wiki/NK_cellshttp://en.wikipedia.org/wiki/NK_cellshttp://en.wikipedia.org/wiki/NK_cellshttp://en.wikipedia.org/wiki/MHC_class_IIhttp://en.wikipedia.org/wiki/MHC_class_IIhttp://en.wikipedia.org/wiki/MHC_II_DMhttp://en.wikipedia.org/wiki/MHC_II_DMhttp://en.wikipedia.org/wiki/MHC_II_DMhttp://en.wikipedia.org/wiki/MHC_II_DQhttp://en.wikipedia.org/wiki/MHC_II_DQhttp://en.wikipedia.org/wiki/MHC_II_DQhttp://en.wikipedia.org/wiki/MHC_II_DRhttp://en.wikipedia.org/wiki/MHC_II_DRhttp://en.wikipedia.org/wiki/MHC_II_DRhttp://en.wikipedia.org/wiki/MHC_II_DPhttp://en.wikipedia.org/wiki/MHC_II_DPhttp://en.wikipedia.org/wiki/MHC_II_DPhttp://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/w/index.php?title=MHC_class_III&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=MHC_class_III&action=edit&redlink=1http://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Complement_component_2http://en.wikipedia.org/wiki/Complement_component_2http://en.wikipedia.org/wiki/Complement_component_2http://en.wikipedia.org/wiki/Complement_component_4http://en.wikipedia.org/wiki/Complement_component_4http://en.wikipedia.org/wiki/Complement_component_4http://en.wikipedia.org/wiki/Complement_factor_Bhttp://en.wikipedia.org/wiki/Complement_factor_Bhttp://en.wikipedia.org/wiki/Complement_factor_Bhttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/TNF-%CE%B1http://en.wikipedia.org/wiki/TNF-%CE%B1http://en.wikipedia.org/wiki/TNF-%CE%B1http://en.wikipedia.org/wiki/TNF-%CE%B1http://en.wikipedia.org/wiki/Heat_shock_proteinshttp://en.wikipedia.org/wiki/Heat_shock_proteinshttp://en.wikipedia.org/wiki/Heat_shock_proteinshttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=3http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=3http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=3http://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=3http://en.wikipedia.org/wiki/Heat_shock_proteinshttp://en.wikipedia.org/wiki/TNF-%CE%B1http://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Complement_factor_Bhttp://en.wikipedia.org/wiki/Complement_component_4http://en.wikipedia.org/wiki/Complement_component_2http://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/w/index.php?title=MHC_class_III&action=edit&redlink=1http://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/CD4http://en.wikipedia.org/wiki/MHC_II_DPhttp://en.wikipedia.org/wiki/MHC_II_DRhttp://en.wikipedia.org/wiki/MHC_II_DQhttp://en.wikipedia.org/wiki/MHC_II_DMhttp://en.wikipedia.org/wiki/MHC_class_IIhttp://en.wikipedia.org/wiki/NK_cellshttp://en.wikipedia.org/wiki/Cytotoxic_T_cellshttp://en.wikipedia.org/wiki/CD8http://en.wikipedia.org/wiki/Tapasinhttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Antigen_processinghttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/MHC_class_Ihttp://en.wikipedia.org/wiki/Chromosome_6http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Mammalshttp://en.wikipedia.org/wiki/Birdhttp://en.wikipedia.org/wiki/Eutheriahttp://en.wikipedia.org/wiki/Eutheriahttp://en.wikipedia.org/wiki/Genotypehttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-belov-2http://en.wikipedia.org/wiki/Marsupialhttp://en.wikipedia.org/wiki/Monodelphis_domesticahttp://en.wikipedia.org/wiki/Opossum


4/12

MHC class I protein molecule

[edit]Class I

MHC I occurs as an chain composed of three domains1, 2, 3. The 1 rests upon a unit of the non-MHC

molecule2 microglobulin(encoded on human chromosome 15). The 3 subunit is transmembrane, anchoring

the MHC class I molecule to the cell membrane. The peptide being presented is held by the floor of

thepeptide-binding groove, in the central region of the 1/2heterodimer(a molecule composed of two

nonidentical subunits). The genetically encoded and expressed sequence of amino acids, the sequence

of residues, of the peptide-binding groove's floor determines which particular peptide residues it binds.[4]

MHC class II protein molecule
http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=4http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=4http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=4http://en.wikipedia.org/wiki/Beta-2_microglobulinhttp://en.wikipedia.org/wiki/Beta-2_microglobulinhttp://en.wikipedia.org/wiki/Beta-2_microglobulinhttp://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/wiki/Heterodimerhttp://en.wikipedia.org/wiki/Heterodimerhttp://en.wikipedia.org/wiki/Heterodimerhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid10935972-3http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid10935972-3http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid10935972-3http://en.wikipedia.org/wiki/File:MHC_Class_2.svghttp://en.wikipedia.org/wiki/File:MHC_Class_2.svghttp://en.wikipedia.org/wiki/File:MHC_Class_1.svghttp://en.wikipedia.org/wiki/File:MHC_Class_1.svghttp://en.wikipedia.org/wiki/File:MHC_Class_2.svghttp://en.wikipedia.org/wiki/File:MHC_Class_1.svghttp://en.wikipedia.org/wiki/File:MHC_Class_2.svghttp://en.wikipedia.org/wiki/File:MHC_Class_1.svghttp://en.wikipedia.org/wiki/File:MHC_Class_2.svghttp://en.wikipedia.org/wiki/File:MHC_Class_1.svghttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid10935972-3http://en.wikipedia.org/wiki/Heterodimerhttp://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/wiki/Beta-2_microglobulinhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=4


5/12

Classical MHC molecules present epitopes to theTCRsof CD8+ T lymphocytes. Nonclassical

molecules (MHC class IB) exhibit limited polymorphism, expression patterns, and presented antigens; this

group is subdivided into a group encoded within MHC loci (e.g., HLA-E, -F, -G) as well as those not (e.g.,

stress ligands such as ULBPs, Rae1, H60); the antigen/ligand for many of these molecules remain unknown,

but they can interact with both CD8+ T cells, NKT cells, and NK cells.

[edit]Class II

MHC class two is formed of two chains, and , each having two domains1 and 2 and 1 and 2each

chain having a transmembrane domain, 2 and 2, respectively, anchoring the MHC class II molecule to the

cell membrane.[5]

The peptide-binding groove is formed of the heterodimer of 1 and 1.

MHC class II molecules in humans have five to six isotypes. Classic molecules present peptides to CD4+

lymphocytes. Nonclassic molecules, accessories, with intracellular functions, are not exposed on cell

membranes, but in internal membranes inlysosomes, normally loading the antigenic peptides onto classic

MHC class II molecules.

[edit]Class III

Class III molecules have physiologic roles unlike classes I and class II, but are encoded between them in the

short arm of human chromosome 6. Class III molecules include several secreted proteins with immune

functions: components of thecomplement system(such as C2, C4, and B factor),cytokines(such asTNF-,

LTA, LTB), andheat shock proteins(hsp).

[edit]Antigen processing and presentation
http://en.wikipedia.org/wiki/TCRhttp://en.wikipedia.org/wiki/TCRhttp://en.wikipedia.org/wiki/TCRhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=5http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=5http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=5http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=6http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=6http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=6http://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/TNF-alphahttp://en.wikipedia.org/wiki/TNF-alphahttp://en.wikipedia.org/wiki/TNF-alphahttp://en.wikipedia.org/wiki/TNF-alphahttp://en.wikipedia.org/wiki/Heat_shock_proteinhttp://en.wikipedia.org/wiki/Heat_shock_proteinhttp://en.wikipedia.org/wiki/Heat_shock_proteinhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=7http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=7http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=7http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=7http://en.wikipedia.org/wiki/Heat_shock_proteinhttp://en.wikipedia.org/wiki/TNF-alphahttp://en.wikipedia.org/wiki/Cytokinehttp://en.wikipedia.org/wiki/Complement_systemhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=6http://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=5http://en.wikipedia.org/wiki/TCR


6/12

MHC class I pathway: Proteins in thecytosolare degraded by theproteasome, liberating peptides internalized

byTAPchannel in theendoplasmic reticulum, there associating with MHC-I molecules freshly synthesized. MHC-I/peptide

complexes enterGolgi apparatus, areglycosylated, enter secratory vesicles, fuse with thecell membrane, and externalize on

the cell membrane interacting with T lymphocytes.

Peptides are processed and presented by two classical pathways:

In MHC class IIphagocytessuch asmacrophagesand immaturedendritic cellsuptake entities

byphagocytosisintophagosomesthoughB cellsexhibit the more generalendocytosisintoendosomes

which fuse withlysosomeswhose acidic enzymes cleave the uptaken protein into many different peptides.

Viaphysicochemical dynamicsin molecular interaction with the particular MHC class II variants borne by

the host, encoded in the host's genome, a particular peptide exhibitsimmunodominanceand loads onto

MHC class II molecules. These are trafficked to and externalized on the cell surface.[6]

In MHC class I any nucleated cell normally presents cytosolic peptides, mostly selfpeptides derived from

protein turnover and defective ribosomal products. During viral infection, intracellular microorganism

infection, or cancerous transformation, such proteins degraded in theproteosomeare as well loaded onto
http://en.wikipedia.org/wiki/Cytosolhttp://en.wikipedia.org/wiki/Cytosolhttp://en.wikipedia.org/wiki/Cytosolhttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Endoplasmic_reticulumhttp://en.wikipedia.org/wiki/Endoplasmic_reticulumhttp://en.wikipedia.org/wiki/Endoplasmic_reticulumhttp://en.wikipedia.org/wiki/Golgi_apparatushttp://en.wikipedia.org/wiki/Golgi_apparatushttp://en.wikipedia.org/wiki/Golgi_apparatushttp://en.wikipedia.org/wiki/Glycosylationhttp://en.wikipedia.org/wiki/Glycosylationhttp://en.wikipedia.org/wiki/Glycosylationhttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Phagocyteshttp://en.wikipedia.org/wiki/Phagocyteshttp://en.wikipedia.org/wiki/Phagocyteshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Phagocytosishttp://en.wikipedia.org/wiki/Phagocytosishttp://en.wikipedia.org/wiki/Phagocytosishttp://en.wikipedia.org/wiki/Phagosomeshttp://en.wikipedia.org/wiki/Phagosomeshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/Endocytosishttp://en.wikipedia.org/wiki/Endocytosishttp://en.wikipedia.org/wiki/Endocytosishttp://en.wikipedia.org/wiki/Endosomeshttp://en.wikipedia.org/wiki/Endosomeshttp://en.wikipedia.org/wiki/Lysosomeshttp://en.wikipedia.org/wiki/Lysosomeshttp://en.wikipedia.org/wiki/Lysosomeshttp://en.wikipedia.org/w/index.php?title=Physicochemical_dynamics&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Physicochemical_dynamics&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Physicochemical_dynamics&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Immunodominance&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Immunodominance&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Immunodominance&action=edit&redlink=1http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-aderem-5http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-aderem-5http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-aderem-5http://en.wikipedia.org/wiki/Proteosomehttp://en.wikipedia.org/wiki/Proteosomehttp://en.wikipedia.org/wiki/Proteosomehttp://en.wikipedia.org/wiki/File:MHC_Class_I_processing.svghttp://en.wikipedia.org/wiki/File:MHC_Class_I_processing.svghttp://en.wikipedia.org/wiki/File:MHC_Class_I_processing.svghttp://en.wikipedia.org/wiki/Proteosomehttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-aderem-5http://en.wikipedia.org/w/index.php?title=Immunodominance&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Physicochemical_dynamics&action=edit&redlink=1http://en.wikipedia.org/wiki/Lysosomeshttp://en.wikipedia.org/wiki/Endosomeshttp://en.wikipedia.org/wiki/Endocytosishttp://en.wikipedia.org/wiki/B_cellshttp://en.wikipedia.org/wiki/Phagosomeshttp://en.wikipedia.org/wiki/Phagocytosishttp://en.wikipedia.org/wiki/Dendritic_cellshttp://en.wikipedia.org/wiki/Macrophageshttp://en.wikipedia.org/wiki/Phagocyteshttp://en.wikipedia.org/wiki/Cell_membranehttp://en.wikipedia.org/wiki/Glycosylationhttp://en.wikipedia.org/wiki/Golgi_apparatushttp://en.wikipedia.org/wiki/Endoplasmic_reticulumhttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Cytosol


7/12

MHC class I molecules and displayed on the cell surface. T lymphocytes can detect a peptide displayed at

0.1%-1% of the MHC molecules.

Table 2. Characteristics of the antigen processing pathways

Characteristic MHC-I pathway MHC-II pathway

Composition of the stable

peptide-MHC complex

Polymorphic chain and 2

microglobulin, peptide bound to

chain

Polymorphic chains and , peptide binds to

both

Types ofantigen presenting

cells(APC)All nucleated cells

Dendritic cells, mononuclear phagocytes,B

lymphocytes, some endothelial cells,

epithelium ofthymus

T lymphocytes able to

respondCytotoxic T lymphocytes(CD8+) Helper T lymphocytes(CD4+)

Origin of antigenic proteins

cytosolicproteins (mostly

synthetized by the cell; may also

enter from the extracellular medium

viaphagosomes)

Proteins present

inendosomesorlysosomes(mostly

internalized from extracellular medium)

Enzymes responsible for

peptide generationCytosolicproteasome

Proteasesfrom endosomes and lysosomes (for

instance,cathepsin)

Location of loading the

peptide on the MHC

molecule

Endoplasmic reticulum Specialized vesicular compartment

Molecules implicated in

transporting the peptides

and loading them on theMHC molecules

TAP(transporter associated with

antigen processing)

DM, invariant chain

[edit]T lymphocyte recognition restrictions

Main article:MHC restriction
http://en.wikipedia.org/wiki/Antigen_presenting_cellhttp://en.wikipedia.org/wiki/Antigen_presenting_cellhttp://en.wikipedia.org/wiki/Antigen_presenting_cellhttp://en.wikipedia.org/wiki/Antigen_presenting_cellhttp://en.wikipedia.org/wiki/Dendritic_cellhttp://en.wikipedia.org/wiki/Dendritic_cellhttp://en.wikipedia.org/wiki/B_lymphocyteshttp://en.wikipedia.org/wiki/B_lymphocyteshttp://en.wikipedia.org/wiki/B_lymphocyteshttp://en.wikipedia.org/wiki/B_lymphocyteshttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Cytotoxic_T_lymphocyteshttp://en.wikipedia.org/wiki/Cytotoxic_T_lymphocyteshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Cytosolhttp://en.wikipedia.org/wiki/Cytosolhttp://en.wikipedia.org/wiki/Phagosomehttp://en.wikipedia.org/wiki/Phagosomehttp://en.wikipedia.org/wiki/Phagosomehttp://en.wikipedia.org/wiki/Endosomehttp://en.wikipedia.org/wiki/Endosomehttp://en.wikipedia.org/wiki/Endosomehttp://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Proteasehttp://en.wikipedia.org/wiki/Proteasehttp://en.wikipedia.org/wiki/Cathepsinhttp://en.wikipedia.org/wiki/Cathepsinhttp://en.wikipedia.org/wiki/Cathepsinhttp://en.wikipedia.org/wiki/Endoplasmic_reticulumhttp://en.wikipedia.org/wiki/Endoplasmic_reticulumhttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=8http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=8http://en.wikipedia.org/wiki/MHC_restrictionhttp://en.wikipedia.org/wiki/MHC_restrictionhttp://en.wikipedia.org/wiki/MHC_restrictionhttp://en.wikipedia.org/wiki/MHC_restrictionhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=8http://en.wikipedia.org/wiki/Transporter_associated_with_antigen_processinghttp://en.wikipedia.org/wiki/Endoplasmic_reticulumhttp://en.wikipedia.org/wiki/Cathepsinhttp://en.wikipedia.org/wiki/Proteasehttp://en.wikipedia.org/wiki/Proteasomehttp://en.wikipedia.org/wiki/Lysosomehttp://en.wikipedia.org/wiki/Endosomehttp://en.wikipedia.org/wiki/Phagosomehttp://en.wikipedia.org/wiki/Cytosolhttp://en.wikipedia.org/wiki/Helper_T_cellshttp://en.wikipedia.org/wiki/Cytotoxic_T_lymphocyteshttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/B_lymphocyteshttp://en.wikipedia.org/wiki/B_lymphocyteshttp://en.wikipedia.org/wiki/Dendritic_cellhttp://en.wikipedia.org/wiki/Antigen_presenting_cellhttp://en.wikipedia.org/wiki/Antigen_presenting_cell


8/12

In their development in thethymus, T lymphocytes are selected to recognize MHC molecules of the host but

not recognize other self antigens. Each T lymphocyte shows dual specificity: The T cell receptor (TCR) does

not recognize selfMHC but only nonselfantigens.

MHC restriction occurs during lymphocyte development in the thymus through a process known as positive

selection. T cells that do not receive a positive survival signal mediated mainly by thymic epithelial cells

presenting selfpeptides bound to MHC molecules to their TCR undergoapoptosis. Positive selection

ensures that mature T cells can functionally recognize MHC molecules in the peripheryelsewhere in the

body.

The TCRs of T lymphocytes recognise onlysequential epitopes, also calledlinear epitopes, of only peptides

and only if coupled within an MHC molecule. (Antibody molecules secreted byactivated B cells, on the other

hand, ligate diverse epitopespeptide,lipid,carbohydrate, andnucleic acidand recognizeconformational

epitopes, which have3Dstructure.)

[edit]MHC in sexual mate selection

Main article:Major Histocompatibility Complex and Sexual Selection

See also:Interpersonal compatibility

MHC molecules enable immune system surveillance of the population of protein molecules in a host cell, and

greater MHC diversity permits greater diversity ofantigen presentation. In 1976 Yamazakiet aldemonstrated

preference by male mice for females of different MHC. Similar results have been obtained with fish.[7]

Some

data find lower rates ofearly pregnancy lossin human couples of dissimilar MHC genes.[8]

It has been proposed that MHC is related to mate choice in some human populations, a theory that has found

support by studies by Ober and colleagues in 1997,[9]

as well as by Chaix and colleagues in 2008.[10]

The

phenomena might be mediated byolfaction, as MHC phenotype appears strongly involved in the strength and

pleasantness of perceived odour of compounds fromsweat. Fatty acidesterssuch asmethyl

undecanoate,methyl decanoate,methyl nonanoate,methyl octanoateandmethyl hexanoateshow strong

connection to MHC.[11]

In 1995Claus Wedekindfound that in a group of female college students who smelled T-shirts worn by male

students for two nights (without deodorant, cologne, or scented soaps), by far most women chose shirts worn

by men of dissimilar MHCs, a preference reversed if the women were on oral contraceptives.[12]

Results of a

2002 experiment likewise suggest HLA-associated odors influence odor preference and may mediate social

cues.[13]

In 2005 in a group of 58 subjects, women were more indecisive when presented with MHCs alike their

own,[14]

although without oral contraceptives, the women showed no particular preference.[15]

[edit]MHC evolutionary diversity
http://en.wikipedia.org/wiki/MHC_restrictionhttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Sequential_epitopehttp://en.wikipedia.org/wiki/Sequential_epitopehttp://en.wikipedia.org/wiki/Sequential_epitopehttp://en.wikipedia.org/wiki/Linear_epitopehttp://en.wikipedia.org/wiki/Linear_epitopehttp://en.wikipedia.org/wiki/Linear_epitopehttp://en.wikipedia.org/wiki/Plasma_cellhttp://en.wikipedia.org/wiki/Plasma_cellhttp://en.wikipedia.org/wiki/Plasma_cellhttp://en.wikipedia.org/wiki/Peptidehttp://en.wikipedia.org/wiki/Peptidehttp://en.wikipedia.org/wiki/Lipidhttp://en.wikipedia.org/wiki/Lipidhttp://en.wikipedia.org/wiki/Lipidhttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Nucleic_acidhttp://en.wikipedia.org/wiki/Nucleic_acidhttp://en.wikipedia.org/wiki/Conformational_epitopehttp://en.wikipedia.org/wiki/Conformational_epitopehttp://en.wikipedia.org/wiki/Conformational_epitopehttp://en.wikipedia.org/wiki/Conformational_epitopehttp://en.wikipedia.org/wiki/Three-dimensional_spacehttp://en.wikipedia.org/wiki/Three-dimensional_spacehttp://en.wikipedia.org/wiki/Three-dimensional_spacehttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=9http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=9http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=9http://en.wikipedia.org/wiki/Major_Histocompatibility_Complex_and_Sexual_Selectionhttp://en.wikipedia.org/wiki/Major_Histocompatibility_Complex_and_Sexual_Selectionhttp://en.wikipedia.org/wiki/Major_Histocompatibility_Complex_and_Sexual_Selectionhttp://en.wikipedia.org/wiki/Interpersonal_compatibilityhttp://en.wikipedia.org/wiki/Interpersonal_compatibilityhttp://en.wikipedia.org/wiki/Interpersonal_compatibilityhttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-boehm-6http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-boehm-6http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-boehm-6http://en.wikipedia.org/wiki/Early_pregnancy_losshttp://en.wikipedia.org/wiki/Early_pregnancy_losshttp://en.wikipedia.org/wiki/Early_pregnancy_losshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Haig-7http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Haig-7http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Haig-7http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ober-8http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ober-8http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ober-8http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-chaix-9http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-chaix-9http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-chaix-9http://en.wikipedia.org/wiki/Olfactionhttp://en.wikipedia.org/wiki/Olfactionhttp://en.wikipedia.org/wiki/Olfactionhttp://en.wikipedia.org/wiki/Sweathttp://en.wikipedia.org/wiki/Sweathttp://en.wikipedia.org/wiki/Sweathttp://en.wikipedia.org/wiki/Estershttp://en.wikipedia.org/wiki/Estershttp://en.wikipedia.org/w/index.php?title=Methyl_undecanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_undecanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_undecanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_undecanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_decanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_decanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_decanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_nonanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_nonanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_nonanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_octanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_octanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_octanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_hexanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_hexanoate&action=edit&redlink=1http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-krefts-10http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-krefts-10http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-krefts-10http://en.wikipedia.org/wiki/Claus_Wedekindhttp://en.wikipedia.org/wiki/Claus_Wedekindhttp://en.wikipedia.org/wiki/Claus_Wedekindhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-wedekind-11http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-wedekind-11http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-wedekind-11http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-jacob-12http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-jacob-12http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-jacob-12http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-santos-13http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-santos-13http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-santos-13http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-14http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-14http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-14http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=10http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=10http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=10http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=10http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-14http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-santos-13http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-jacob-12http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-wedekind-11http://en.wikipedia.org/wiki/Claus_Wedekindhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-krefts-10http://en.wikipedia.org/w/index.php?title=Methyl_hexanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_octanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_nonanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_decanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_undecanoate&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Methyl_undecanoate&action=edit&redlink=1http://en.wikipedia.org/wiki/Estershttp://en.wikipedia.org/wiki/Sweathttp://en.wikipedia.org/wiki/Olfactionhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-chaix-9http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ober-8http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Haig-7http://en.wikipedia.org/wiki/Early_pregnancy_losshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-boehm-6http://en.wikipedia.org/wiki/Antigen_presentationhttp://en.wikipedia.org/wiki/Interpersonal_compatibilityhttp://en.wikipedia.org/wiki/Major_Histocompatibility_Complex_and_Sexual_Selectionhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=9http://en.wikipedia.org/wiki/Three-dimensional_spacehttp://en.wikipedia.org/wiki/Conformational_epitopehttp://en.wikipedia.org/wiki/Conformational_epitopehttp://en.wikipedia.org/wiki/Nucleic_acidhttp://en.wikipedia.org/wiki/Carbohydratehttp://en.wikipedia.org/wiki/Lipidhttp://en.wikipedia.org/wiki/Peptidehttp://en.wikipedia.org/wiki/Plasma_cellhttp://en.wikipedia.org/wiki/Linear_epitopehttp://en.wikipedia.org/wiki/Sequential_epitopehttp://en.wikipedia.org/wiki/Apoptosishttp://en.wikipedia.org/wiki/Thymus


9/12

Mostmammalshave MHC variants similar to those of humans, who bear greatallelic diversity, especially

among the nine classical genesseemingly due largely togene duplicationthough human MHC regions have

manypseudogenes. The most diverse loci, namely HLA-A, HLA-B, and HLA-DRB1, have roughly 1000, 1600,

and 870 known alleles, respectively. Many HLA alleles are ancient, sometimes of greaterhomologyto a

chimpanzee MHC alleles than to some other human alleles of the same gene.

MHC allelic diversity has challengedevolutionary biologistsfor explanation. Most positbalancing

selection[seepolymorphism (biology)], which is anynatural selectionprocess whereby no single allele is

absolutely most fit, such asfrequency-dependent selectionandheterozygote advantage. Recent models

suggest that a high number of alleles is implausible via heterozygote advantage alone.

Pathogenic co-evolution, a counter-hypothesis, posits that common alleles are under greatest pathogenic

pressure, driving positive selection of uncommon allelesmoving targets, so to say, for pathogens. As

pathogenic pressure on the previously common alleles decreases, their frequency in the population stabilizes,

and remain circulating in a large population. Despite great MHC polymorphism at the population level, an

individual bears at most 18 MHC I or II alleles.

Relatively low MHC diversity has been observed in thecheetah(Acinonyx jubatus),[16]

Eurasian beaver(Castor

fiber),[17]

andgiant panda(Ailuropoda melanoleuca).[18]

In 2007 low MHC diversity was attributed a role in

disease susceptibility in theTasmanian devil(Sarcophilus harrisii), native to the isolated island ofTasmania,

such that an antigen of a transmissible tumor, involved indevil facial tumour disease, appears to be recognized

as a self antigen.[19]

To offsetinbreeding, efforts to sustain genetic diversity in populations of endangered

species and of captive animals have been suggested.

[edit]MHC in transplant rejection

In a transplant procedure, as of an organ orstem cells, MHC molecules act themselves asantigensand can

provoke immune response in the recipientthus transplant rejection. MHC molecules were identified and

named after their role intransplantrejection between mice of different strains, though it took over 20 years to

clarify MHC's role in presenting peptide antigens tocytotoxic T lymphocytes(CTLs).[20]

Each human cell expresses six MHC class I alleles (one HLA-A, -B, and -C allele from each parent) and six to

eight MHC class 2 alleles (one HLA-DP and -DQ, and one or two HLA-DR from each parent, and combinations

of these). The MHC variation in the human population is high, at least 350 alleles for HLA-A genes, 620 alleles

for HLA-B, 400 alleles for DR, and 90 alleles for DQ. Any two individuals not identical twins express differing

MHC molecules. All MHC molecules can mediate transplant rejection, but HLA-C and HLA-DP, showing low

polymorphism, seem least important.

When maturing in thethymusgland,T lymphocytesare selected for their T cell receptors (TCR) incapacity to

recognize self antigens. Yet T lymphocytes can react against the donor MHC'speptide-binding groove, the
http://en.wikipedia.org/wiki/Mammalhttp://en.wikipedia.org/wiki/Mammalhttp://en.wikipedia.org/wiki/Mammalhttp://en.wikipedia.org/wiki/Gene_poolhttp://en.wikipedia.org/wiki/Gene_poolhttp://en.wikipedia.org/wiki/Gene_poolhttp://en.wikipedia.org/wiki/Gene_duplicationhttp://en.wikipedia.org/wiki/Gene_duplicationhttp://en.wikipedia.org/wiki/Pseudogenehttp://en.wikipedia.org/wiki/Pseudogenehttp://en.wikipedia.org/wiki/Pseudogenehttp://en.wikipedia.org/wiki/Homologyhttp://en.wikipedia.org/wiki/Homologyhttp://en.wikipedia.org/wiki/Homologyhttp://en.wikipedia.org/wiki/Evolutionary_biologyhttp://en.wikipedia.org/wiki/Evolutionary_biologyhttp://en.wikipedia.org/wiki/Evolutionary_biologyhttp://en.wikipedia.org/wiki/Balancing_selectionhttp://en.wikipedia.org/wiki/Balancing_selectionhttp://en.wikipedia.org/wiki/Balancing_selectionhttp://en.wikipedia.org/wiki/Balancing_selectionhttp://en.wikipedia.org/wiki/Polymorphism_(biology)http://en.wikipedia.org/wiki/Polymorphism_(biology)http://en.wikipedia.org/wiki/Polymorphism_(biology)http://en.wikipedia.org/wiki/Natural_selectionhttp://en.wikipedia.org/wiki/Natural_selectionhttp://en.wikipedia.org/wiki/Natural_selectionhttp://en.wikipedia.org/wiki/Frequency-dependent_selectionhttp://en.wikipedia.org/wiki/Frequency-dependent_selectionhttp://en.wikipedia.org/wiki/Frequency-dependent_selectionhttp://en.wikipedia.org/wiki/Heterozygote_advantagehttp://en.wikipedia.org/wiki/Heterozygote_advantagehttp://en.wikipedia.org/wiki/Heterozygote_advantagehttp://en.wikipedia.org/wiki/Cheetahhttp://en.wikipedia.org/wiki/Cheetahhttp://en.wikipedia.org/wiki/Cheetahhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Castro-Prieto-15http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Castro-Prieto-15http://en.wikipedia.org/wiki/Eurasian_beaverhttp://en.wikipedia.org/wiki/Eurasian_beaverhttp://en.wikipedia.org/wiki/Eurasian_beaverhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Babik-16http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Babik-16http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Babik-16http://en.wikipedia.org/wiki/Giant_pandahttp://en.wikipedia.org/wiki/Giant_pandahttp://en.wikipedia.org/wiki/Giant_pandahttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid17555583-17http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid17555583-17http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid17555583-17http://en.wikipedia.org/wiki/Tasmanian_devilhttp://en.wikipedia.org/wiki/Tasmanian_devilhttp://en.wikipedia.org/wiki/Tasmanian_devilhttp://en.wikipedia.org/wiki/Tasmaniahttp://en.wikipedia.org/wiki/Tasmaniahttp://en.wikipedia.org/wiki/Tasmaniahttp://en.wikipedia.org/wiki/Devil_facial_tumour_diseasehttp://en.wikipedia.org/wiki/Devil_facial_tumour_diseasehttp://en.wikipedia.org/wiki/Devil_facial_tumour_diseasehttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Siddle-18http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Siddle-18http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Siddle-18http://en.wikipedia.org/wiki/Inbreedinghttp://en.wikipedia.org/wiki/Inbreedinghttp://en.wikipedia.org/wiki/Inbreedinghttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=11http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=11http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=11http://en.wikipedia.org/wiki/Stem_cellshttp://en.wikipedia.org/wiki/Stem_cellshttp://en.wikipedia.org/wiki/Stem_cellshttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Cytotoxic_T_lymphocyteshttp://en.wikipedia.org/wiki/Cytotoxic_T_lymphocyteshttp://en.wikipedia.org/wiki/Cytotoxic_T_lymphocyteshttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS_Ch.10-19http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS_Ch.10-19http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS_Ch.10-19http://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/T_lymphocytehttp://en.wikipedia.org/wiki/T_lymphocytehttp://en.wikipedia.org/wiki/T_lymphocytehttp://en.wikipedia.org/wiki/TCRhttp://en.wikipedia.org/wiki/TCRhttp://en.wikipedia.org/wiki/TCRhttp://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Peptide-binding_groove&action=edit&redlink=1http://en.wikipedia.org/wiki/TCRhttp://en.wikipedia.org/wiki/T_lymphocytehttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS_Ch.10-19http://en.wikipedia.org/wiki/Cytotoxic_T_lymphocyteshttp://en.wikipedia.org/wiki/Organ_transplanthttp://en.wikipedia.org/wiki/Antigenhttp://en.wikipedia.org/wiki/Stem_cellshttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=11http://en.wikipedia.org/wiki/Inbreedinghttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Siddle-18http://en.wikipedia.org/wiki/Devil_facial_tumour_diseasehttp://en.wikipedia.org/wiki/Tasmaniahttp://en.wikipedia.org/wiki/Tasmanian_devilhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-pmid17555583-17http://en.wikipedia.org/wiki/Giant_pandahttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Babik-16http://en.wikipedia.org/wiki/Eurasian_beaverhttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-Castro-Prieto-15http://en.wikipedia.org/wiki/Cheetahhttp://en.wikipedia.org/wiki/Heterozygote_advantagehttp://en.wikipedia.org/wiki/Frequency-dependent_selectionhttp://en.wikipedia.org/wiki/Natural_selectionhttp://en.wikipedia.org/wiki/Polymorphism_(biology)http://en.wikipedia.org/wiki/Balancing_selectionhttp://en.wikipedia.org/wiki/Balancing_selectionhttp://en.wikipedia.org/wiki/Evolutionary_biologyhttp://en.wikipedia.org/wiki/Homologyhttp://en.wikipedia.org/wiki/Pseudogenehttp://en.wikipedia.org/wiki/Gene_duplicationhttp://en.wikipedia.org/wiki/Gene_poolhttp://en.wikipedia.org/wiki/Mammal


10/12

variable region of MHC holding the presented antigen'sepitopefor recognition by TCR, the matchingparatope.

T lymphocytes of the recipient take the incompatible peptide-binding groove as nonself antigen. The T

lymphocytes' recognition of the foreign MHC as self isallorecognition.

Transplant rejection has two types known as mediated by MHC (HLA):

Hyperacute rejection occurs when, before the trasplantation, the recipient has preformed anti-HLA

antibodies, perhaps by previous blood transfusions (donor tissue that includes lymphocytes expressing

HLA molecules), by anti-HLA generated during pregnancy (directed at the father's HLA displayed by the

fetus), or by previous transplantation;

Acute humoral rejection and chronic disfunction occurs when the recipient's anti-HLA antibodies form

directed at HLA molecules present onendothelial cellsof the transplanted tissue.

In either situation, immunity is directed at the transplanted organ, sustaining lesions. A cross-reaction

testbetween potential donor cells and recipient serum seeks to detect presence of preformed anti-HLA

antibodies in the potential recipient that recognize donor HLA molecules, so as to prevent hyperacute rejection.

In normal circumstances, compatibility between HLA-A, -B, and -DR molecules is assessed. The higher the

number of incompatibilities, the lower the five-year survival rate. Global databases of donor information

enhance the search for compatible donors.

[edit]HLA biology

Codominant expression of HLA genes.

Main article:Human leukocyte antigen
http://en.wikipedia.org/wiki/Epitopehttp://en.wikipedia.org/wiki/Epitopehttp://en.wikipedia.org/wiki/Epitopehttp://en.wikipedia.org/wiki/Paratopehttp://en.wikipedia.org/wiki/Paratopehttp://en.wikipedia.org/wiki/Paratopehttp://en.wikipedia.org/wiki/Allorecognitionhttp://en.wikipedia.org/wiki/Allorecognitionhttp://en.wikipedia.org/wiki/Allorecognitionhttp://en.wikipedia.org/wiki/Endothelial_cellshttp://en.wikipedia.org/wiki/Endothelial_cellshttp://en.wikipedia.org/wiki/Endothelial_cellshttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=12http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=12http://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=12http://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/File:MHC_expression.svghttp://en.wikipedia.org/wiki/File:MHC_expression.svghttp://en.wikipedia.org/wiki/File:MHC_expression.svghttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/w/index.php?title=Major_histocompatibility_complex&action=edit&section=12http://en.wikipedia.org/wiki/Endothelial_cellshttp://en.wikipedia.org/wiki/Allorecognitionhttp://en.wikipedia.org/wiki/Paratopehttp://en.wikipedia.org/wiki/Epitope


11/12

Human MHC class I and II are also called human leukocyte antigen(HLA). To clarify the usage, some of the

biomedical literature uses HLA to refer specifically to the HLA protein molecules and reserves MHC for the

region of the genome that encodes for this molecule, but this is not a consistent convention.

The most intensely studied HLA genes are the nine so-called classical MHC genes:HLA-A,HLA-B,HLA-

C,HLA-DPA1,HLA-DPB1,HLA-DQA1,HLA-DQB1,HLA-DRA, andHLA-DRB1. In humans, the MHC is

divided into three regions: classes I, II, and III. The A, B, C, E, F, and G genes belong to MHC class I, whereas

the six D genes belong to class II.

MHC genes are expressed in codominant fashion.[5]

This means that thealleles(variants) inherited from both

progenitors are expressed in equivalent way:

As there are 3 Class-I genes, named in humans HLA-A, HLA-B and HLA-C, and as each person inherits a

set of genes from each progenitor, that means that any cell in an individual can express 6 different types of

MHC-I molecules (see figure).

In the Class-IIlocus, each person inherits a couple of genes HLA-DP (DPA1 and DPA2, which encode

and chains), a couple of genes HLA-DQ (DQA1 and DQA2, for and chains), one gene HLA-DR

(DRA1) and one or two genes HLA-DR (DRB1 and DRB3, -4 o -5). That means that

oneheterozygousindividual can inherit 6 or 8 Class-II alleles, three or four from each progenitor.

The set of alleles that is present in each chromosome is called MHChaplotype. In humans, each HLA allele is

named with a number. For instance, for a given individual, his haplotype might be HLA-A2, HLA-B5, HLA-DR3,

etc... Each heterozygous individual will have two MHC haplotypes, one in each chromosome (one of paternal

origin and the other of maternal origin).

The MHC genes are highly polymorphic; this means that there are many different alleles in the different

individuals inside a population. The polymorphism is so high that in a mixed population (non-endogamic) there

are not two individuals with exactly the same set of MHC genes and molecules, with the exception ofidentical

twins.

The polymorphic regions in each allele are located in the region for peptide contact, which is going to be

displayed to the lymphocyte. For this reason, the contact region for each allele of MHC molecule is highly

variable, as the polymorphic residues of the MHC will create specific clefts in which only certain types of

residues of the peptide can enter. This imposes a very specific link between the MHC molecule and the

peptide, and it implies that each MHC variant will be able to bind specifically only those peptides that are able

to properly enter in the cleft of the MHC molecule, which is variable for each allele. In this way, the MHC

molecules have a broad specificity, because they can bind many, but not all types of possible peptides. This is

an essential characteristic of MHC molecules: In a given individual, it is enough to have a few different

molecules to be able to display a high variety of peptides.
http://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/Human_leukocyte_antigenhttp://en.wikipedia.org/wiki/HLA-Ahttp://en.wikipedia.org/wiki/HLA-Ahttp://en.wikipedia.org/wiki/HLA-Ahttp://en.wikipedia.org/wiki/HLA-Bhttp://en.wikipedia.org/wiki/HLA-Bhttp://en.wikipedia.org/wiki/HLA-Bhttp://en.wikipedia.org/wiki/HLA-Chttp://en.wikipedia.org/wiki/HLA-Chttp://en.wikipedia.org/wiki/HLA-Chttp://en.wikipedia.org/wiki/HLA-Chttp://en.wikipedia.org/wiki/HLA-DPA1http://en.wikipedia.org/wiki/HLA-DPA1http://en.wikipedia.org/wiki/HLA-DPA1http://en.wikipedia.org/wiki/HLA-DPB1http://en.wikipedia.org/wiki/HLA-DPB1http://en.wikipedia.org/wiki/HLA-DPB1http://en.wikipedia.org/wiki/HLA-DQA1http://en.wikipedia.org/wiki/HLA-DQA1http://en.wikipedia.org/wiki/HLA-DQA1http://en.wikipedia.org/wiki/HLA-DQB1http://en.wikipedia.org/wiki/HLA-DQB1http://en.wikipedia.org/wiki/HLA-DQB1http://en.wikipedia.org/wiki/HLA-DRAhttp://en.wikipedia.org/wiki/HLA-DRAhttp://en.wikipedia.org/wiki/HLA-DRAhttp://en.wikipedia.org/wiki/HLA-DRB1http://en.wikipedia.org/wiki/HLA-DRB1http://en.wikipedia.org/wiki/HLA-DRB1http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Locushttp://en.wikipedia.org/wiki/Locushttp://en.wikipedia.org/wiki/Locushttp://en.wikipedia.org/wiki/Heterozygoushttp://en.wikipedia.org/wiki/Heterozygoushttp://en.wikipedia.org/wiki/Heterozygoushttp://en.wikipedia.org/wiki/Haplotypehttp://en.wikipedia.org/wiki/Haplotypehttp://en.wikipedia.org/wiki/Haplotypehttp://en.wikipedia.org/wiki/Endogamyhttp://en.wikipedia.org/wiki/Endogamyhttp://en.wikipedia.org/wiki/Endogamyhttp://en.wikipedia.org/wiki/Twinhttp://en.wikipedia.org/wiki/Twinhttp://en.wikipedia.org/wiki/Twinhttp://en.wikipedia.org/wiki/Twinhttp://en.wikipedia.org/wiki/Twinhttp://en.wikipedia.org/wiki/Twinhttp://en.wikipedia.org/wiki/Endogamyhttp://en.wikipedia.org/wiki/Haplotypehttp://en.wikipedia.org/wiki/Heterozygoushttp://en.wikipedia.org/wiki/Locushttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Major_histocompatibility_complex#cite_note-ABBAS-4http://en.wikipedia.org/wiki/HLA-DRB1http://en.wikipedia.org/wiki/HLA-DRAhttp://en.wikipedia.org/wiki/HLA-DQB1http://en.wikipedia.org/wiki/HLA-DQA1http://en.wikipedia.org/wiki/HLA-DPB1http://en.wikipedia.org/wiki/HLA-DPA1http://en.wikipedia.org/wiki/HLA-Chttp://en.wikipedia.org/wiki/HLA-Chttp://en.wikipedia.org/wiki/HLA-Bhttp://en.wikipedia.org/wiki/HLA-Ahttp://en.wikipedia.org/wiki/Human_leukocyte_antigen


12/12

On the other hand, inside a population, the presence of many different alleles ensures there will always be an

individual with a specific MHC molecule able to load the correct peptide to recognize a specific microbe. The

evolution of the MHC polymorphism ensures that a population will not succumb to a new pathogen or a

mutated one, because at least some individuals will be able to develop an adequate immune response to win

over the pathogen. The variations in the MHC molecules (responsible for the polymorphism) are the result of

the inheritance of different MHC molecules, and they are not induced byrecombination, as it is the case for the

antigenreceptors.

Because of the high levels ofallelicdiversity found within its genes, MHC has also attracted the attention of

manyevolutionarybiologists.
http://en.wikipedia.org/wiki/Recombinationhttp://en.wikipedia.org/wiki/Recombinationhttp://en.wikipedia.org/wiki/Recombinationhttp://en.wikipedia.org/wiki/Immune_receptorhttp://en.wikipedia.org/wiki/Immune_receptorhttp://en.wikipedia.org/wiki/Immune_receptorhttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Evolutionhttp://en.wikipedia.org/wiki/Evolutionhttp://en.wikipedia.org/wiki/Evolutionhttp://en.wikipedia.org/wiki/Evolutionhttp://en.wikipedia.org/wiki/Allelehttp://en.wikipedia.org/wiki/Immune_receptorhttp://en.wikipedia.org/wiki/Recombination

major his to compatibility complex

Documents