antigen processing and presentation, self mhc restriction
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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
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