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Antigen presentation to T lymphocytes Chapter 5

Antigen presentation to T lymphocytes Chapter 5. 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.

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Antigen presentation to T lymphocytes Chapter 5

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  1. Antigen presentation to T lymphocytesChapter 5

  2. 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

  3. 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

  4. Antigens are derived from cytosolic or vesicular compartments

  5. Antigen processing for MHC I • Cytoplasmic proteins are degraded by the proteasome

  6. Antigen processing for MHC I • The proteasome exists in two forms: • Constitutive • Immunoproteasome (interferon-inducible)

  7. 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

  8. Antigen processing for MHC I

  9. MHC I antigen processing animation

  10. Antigens are derived from cytosolic or vesicular compartments

  11. Antigen processing for MHC II • Extracellular proteins are processed in endosomes by hydrolytic enzymes

  12. MHC II expression pattern in cells Lysosome marker GFP-tagged MHCII Both signals Wubboltz et al, J Cell Biol 135:611-622, 1996

  13. 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

  14. Antigen processing for MHC II

  15. MHC II antigen processing animation

  16. GFP-tagged Mycobacterium tuberculosis Acidotropic dye (fluoresces in acidic vesicles) Rap = rapamycin (antibiotic) Guitierrez et al, Cell 119:753-796, 2004

  17. 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

  18. Organization of HLA genes

  19. Polymorphism of HLA genes # of alleles (as of 1/04)

  20. Polygeny and polymorphism of HLA

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