antigen presentation to t lymphocytes chapter 5. objectives explain and illustrate the mechanisms of...
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Objectives
• Explain and illustrate the mechanisms of antigen processing for presentation on – MHC I– MHC II
• Describe how polygeny and polymorphism contribute to variation in MHC in a population
Antigen processing
• Antigen processing: degradation of proteins into peptides that can be presented on MHC I or MHC II
– MHC I presents peptides derived from cytoplasmic antigens
– MHC II presents peptides derived from extracellular or intravesicular antigens
Antigens are derived from cytosolic or vesicular
compartments
Antigen processing for MHC I
• The proteasome exists in two forms:– Constitutive– Immunoproteasome
(interferon-inducible)
Antigen processing for MHC I
• MHC I is a transmembrane protein made in the ER
• Cytoplasm-derived peptides must be transported into the ER to bind MHC I
Antigens are derived from cytosolic or vesicular
compartments
Antigen processing for MHC II
•Extracellular proteins are processed in endosomes by hydrolytic enzymes
MHC II expression pattern in cells
Wubboltz et al, J Cell Biol 135:611-622, 1996
Lysosome markerGFP-tagged MHCII
Both signals
Antigen processing for MHC II
• The invariant chain (Ii) blocks the MHC II peptide-binding cleft while it is in the ER
• Acid proteases cleave Ii but leave a fragment (CLIP) in the peptide-binding groove
GFP-tagged Mycobacterium tuberculosisAcidotropic dye (fluoresces in acidic vesicles)
Guitierrez et al, Cell 119:753-796, 2004Rap = rapamycin (antibiotic)
Humans have many variants of MHC I and II
• Human MHC proteins are called Human Leukocyte Antigen (HLA) class I and class II
• HLA molecules are polygenic and highly polymorphic
• Each HLA I or HLA II has a different range of peptide binding specificities