Antigen Processing and Presentation, Self MHC

Restriction

What Does The B Cell Immunoglobulin (Ig) Receptor

Recognize?1. Proteins (conformational determinants,

denatured or proteolyzed determinants)2. Nucleic acids3. Polysaccharides4. Some lipids5. Small chemicals (haptens)

Antigen Processing and Presentation

• Fragmentation of protein into peptides• Association of peptide with an MHC

molecule• Transport to cell surface for expression• Different cellular pathways for

association of peptide with MHC class I and class II molecules

Class I MHC Pathway

Viral protein is madeon cytoplasmic

ribosomes

Proteasome degrades protein topeptides

Peptide transporterprotein moves peptide into ER

MHC class I alpha and beta proteinsare made on the rER

Peptide associateswith MHC-I complex

Peptide with MHCgoes to Golgi body

Peptide passeswith MHC from Golgi

body to surface

Peptide is presentedby MHC-I to CD8cytotoxic T cell

Golgi body

rER

Globular viralprotein - intact

Plasma membrane

Class II MHC Pathway

Globular protein

Endocytosis

Protein is processed topeptides in endosome

or lysosome

Endosome

Lysosome

Fusion of endosomeand exocytic vesicle

Endoplasmic reticulum

Class II MHCSynthesis

3 chains: α,β and Ii

Golgibody

Exocytic vesicle fuseswith endosome

releasing Ii from αβ dimer

α

β Ii

Immunodominantpeptide binds

to class II MHC

Endosome fuses withplasma membrane

Peptide MHC-II complex is presentedto CD4 helper T cell CD4 helper T cell

Plasma membrane

Structure of Class I MHC

NH2

Alloantigenicsites

CHO

NH2

COOH

COOH

P

α1

α2

α3

β2

OH

Plasma membrane

Disulfide bridge

Papain cleavage

Cytoplasm

NH2

Structure of Class II MHC

Plasma membrane

Cytoplasm

CHO

CHO

CHO

NH2 NH2

COOH COOH

α1

α2 β2

β1

Points Concerning Antigen Processing and Presentation

1. Location of pathogen • viruses in cytosol, MHC class I pathway, Tc

response • extracellular bacteria, MHC class II

pathway, TH2 response, Ab formation • intracellular bacteria, MHC class II pathway,

TH1 response

Points Concerning Antigen Processing and Presentation

2. Peptides derived from both self and non-self proteins can associate with MHC class I and class II molecules.

3. Chemical nature of MHC groove determines which peptides it will bind.

Aspects of MHC

1. MHC molecules are membrane-bound. Recognition by T cells requires cell-cell contact.

2. Peptide from cytosol associates with class I MHC and is recognized by Tc cells. Peptide from vesicles associates with class II MHC and is recognized by TH cells.

Aspects of MHC (continued)3. Although there is a high degree of

polymorphism for a species, an individual has maximum of six different class I MHC products and only slightly more class II MHC products.

A peptide must associate with a given MHC of that individual, otherwise no immune response can occur. That is one level of control.

Aspects of MHC (continued)4. Mature T cells must have a T cell

receptor that recognizes the peptide associated with MHC. This is the second level of control.

5. Each MHC molecule has only one binding site. The different peptides a given MHC molecule can bind all types to the same site, but only one at a time.

Animation oh MHC I & II

Lymphatic Tissues

Primary Lymph Tissues

Secondary Lymph Tissues

BoneMarrow

Thymus Gland SpleenLymph Nodes

Bursa of Fabrices

Bayer’sPatches

Types of AbsAgainst Same Ag

Allotype IdiotypeIsotype

Different Variable For the same Ag On Same Class

Different Amimals

e.g.: Horse to Human

Different classesIgG, IgM, IgA

IgD, IgE