antigen processing and presentation, self mhc restriction
DESCRIPTION
Antigen Processing and Presentation, Self MHC Restriction. What Does The B Cell Immunoglobulin (Ig) Receptor Recognize?. Proteins (conformational determinants, denatured or proteolyzed determinants) Nucleic acids Polysaccharides Some lipids Small chemicals (haptens). - PowerPoint PPT PresentationTRANSCRIPT
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Antigen Processing and Presentation, Self MHC
Restriction
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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)
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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
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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
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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
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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
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Structure of Class II MHC
Plasma membrane
Cytoplasm
CHO
CHO
CHO
NH2 NH2
COOH COOH
α1
α2 β2
β1
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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
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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.
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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.
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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.
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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.
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Animation oh MHC I & II
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Lymphatic Tissues
Primary Lymph Tissues
Secondary Lymph Tissues
BoneMarrow
Thymus Gland SpleenLymph Nodes
Bursa of Fabrices
Bayer’sPatches
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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