mhc molecule

28
Presented By; B. Om Preeti Singh (M.V.Sc. Microbiology) C.V.Sc. & A.H ,N.D.U.A&T. Faizabad, U.P.

Upload: preeti337

Post on 24-May-2015

547 views

Category:

Education


1 download

DESCRIPTION

MAJOR HISTO COMPATABILITY

TRANSCRIPT

Page 1: MHC MOLECULE

Presented By;

B. Om Preeti Singh

(M.V.Sc. Microbiology)

C.V.Sc. & A.H ,N.D.U.A&T. Faizabad, U.P.

Page 2: MHC MOLECULE
Page 3: MHC MOLECULE

MHC

◦ Cluster of genes found in all mammals

◦ MHC Act As Antigen Presenting receptors and are called as histocompatabilitymolecules.

involved in

◦ cell-cell interaction◦ antigen presentation◦ recognition of self-nonself molecules

- Participant in both humoral and cell-mediated immunity

Page 4: MHC MOLECULE

In Human, MHC Is Found On Chromosome 6◦ Referred to as HLA complex

HLA genes are very diverse (polymorphic)

i.e. there are many alleles of the class I and II genes

In Mice, MHC Is Found On Chromosome 17◦ Referred to as H-2 complex

In dogs – DLA complex

In rabbits – RLA complex

In chickens – B complex

In bovines – BoLA and so forth

Page 5: MHC MOLECULE

Class I MHC ◦ almost all nucleated cells◦ antigen presentation to cytotoxic T cells◦ Found In Regions A, B and C In Humans (K and D In

Mice)

Class II MHC ◦ on antigen-presenting cells◦ antigen presentation to helper T cells◦ Found In Regions DR, DP and DQ (IA and IE In Mice)

These molecules are cell-surface glycoproteins

class I and Class II MHC Share Structural Features

◦ Both involved in APC

Page 6: MHC MOLECULE
Page 7: MHC MOLECULE

Class III- MHC genes

- secreted proteins( Products that include secreted proteins that have immune functions.)◦ complement components◦ Inflammation

Class III MHC Have No Structural Similarity To Class I and II

Page 8: MHC MOLECULE
Page 9: MHC MOLECULE

Identified by cytotoxic T cells

a chain noncovalently attached to b2-microglobulin

association required for expression of class I molecules

on the cell surface

Peptide-binding cleft located on top of the surface of

Class I – between a1 and a2

a chain is a transmembrane glycoprotein

Page 10: MHC MOLECULE
Page 11: MHC MOLECULE
Page 12: MHC MOLECULE

a chain

◦ a1, a2, a3 – on outside of membrane

◦ transmembrane domain

◦ cytoplasmic tail

b2-microglobulin

◦ similar to a3

◦ no transmembrane region

Page 13: MHC MOLECULE

Total no . Of class I loci varies

In humans about 20

In mice 30, but all these are not functional

In humans the functional loci are A,B,C,

In mice K,D

Others are pseudo genes that cannot be expressed.

Page 14: MHC MOLECULE
Page 15: MHC MOLECULE

* Between the class I and class II gene loci, there is a third locus (Class III)

* This locus contains genes encoding tumor necrosis factor, lymphotoxin and two complement components(C2 and C4)

* Class III antigens do not participate in MHC restriction or graft rejection

Page 16: MHC MOLECULE

* Class I MHC antigens are : HLA-A, HLA-B and HLA-C

* These antigens are glycoproteins found on surfaces of all nucleotide human cells and on platelets

* HLA-A contains 24 different antigenic specificities,

HLA-B contains 52 and HLA-C contains 11

* Class I MHC antigens are involved of MHC restriction of cell mediated cytotoxicity

Page 17: MHC MOLECULE

* Endogenously processed cytosolic peptides in virus infected cells or tumor cells are transported to the surface of the cells

* They bind to MHC I molecules to be recognized by cytotoxic T-cells which then kill these cells

* In other words;

T-cells are only activated when they recognize both antigen and class I MHC molecules in association

Page 18: MHC MOLECULE

Recognized by helper T cells

HLA-DR

Structure

◦ External domains, transmembrane segment and cytoplasmic

anchor

4 exterior domains – a1, a2, b1, b2

Page 19: MHC MOLECULE
Page 20: MHC MOLECULE

Class II antigens are: HLA-DP, HLA-DQ, HLA-DR antigens

These antigens are glycoproteins found on the surface of macrophages, B-cells, Dentritic cells, langerhans cells of skin and activated T cells

HLA-DP contain 6 different antigenic specificities, HLA-DQ contains 9 and HLA-DR contains 20

Page 21: MHC MOLECULE

Helper T-cells recognize antigens on antigen-presenting cells only when the antigens are presented on the surface of cells in association with class II MHC

* Class II antigens react with the CD4 molecule on the helper T-cells which secrete cytokines

Page 22: MHC MOLECULE

MHC Class I MHC Class II

Nomenclature HLA-A, HLA-B, HLA-C HLA-DP, HLA-DQ,

HLA-DR

Found on All nucleated somatic cells

Macrophages, B-cells, Dentritic cells,

langerhans cells of skin and activated T cells

Recognized by CD8 TC cells CD4 TH cells

Functions Presentation of Ag to TCcells leading to

elimination of tumor or infected host cell

Presentation of Ag to THcells which secrete

cytokines

Page 23: MHC MOLECULE

MHC –Clinical significance

Page 24: MHC MOLECULE

both class I and class II molecules can induce a response that leads to graft rejection

MHC antigens also appear to play a role in development of auto diseases

both class I and class II molecules play a major role in antigen presentation

Page 25: MHC MOLECULE

They essentially determine the types of peptides to which an individual can mount an immune response.

Although the MHC molecules typically have a broad binding capacity, small biochemical differences in these proteins are responsible for differences seen in the ability to react to a specific antigen.

Thus individual’s MHC type for numerous reasons must be known.

Page 26: MHC MOLECULE

For eg. hepatitis B

Do not have the genetic capacity to respond. But, presence of a particular MHC protein may conferadditional protection.

vaccines containing certain amino acid sequences that serve as immunodominantepitopes can be specifically developed.

This might avoid the risk associated with using live organisms.

Page 27: MHC MOLECULE

Additionally, if an individual suffers from allergies, knowing a person’s MHC type may predict the types of allergens

It is likely that knowledge of the MHCmolecules will affect many areas of patient care in the future.

Page 28: MHC MOLECULE

THANK U