MHC I, II, Ag-Presentation Kuby, Immunology , 5 th Edition Chapters 7 and 8

1. MHC I, II, Ag-PresentationKuby, Immunology, 5th EditionChapters 7 and 8 Jim Collawn MCLM 350 jcollawn@uab.edu

2. Study Objectives • Compare and contrast the structures of MHC class I and class II molecules. • How do the peptide binding sites differ between them? • What is the biological function of these molecules? • What is the relationship between MHC molecules and helper and cytotoxic T cell responses? • 5. Compare and contrast class I and class II MHC-restricted • responses with regard to • A. source of antigens • B. antigen processing requirements • C. role of chaperones • D. types of T cell involved • 6. Discuss the invariant chain’s role in the demarcation between class I and class II MHC-restricted responses. • 7. Discuss DMA and DMB’s possible role in antigen processing.

3. Introduction • Humoral versus cellular responses • Types of T cells • Structural organization of MHC class I and II molecules • Subunit compositions • MHC domain structure • Peptide binding sites on MHC molecules • Peptide antigen sequences and patterns • MHC polymorphisms • Associations of HLA alleles with Human Disease • Antigen processing and presentation • MHC restriction • Antigen processing • Processing and presentation of exogenous and • endogenous antigens • Role of chaperones in antigen processing and presentation • Class I chaperones • TAP genes • Calnexin • Tapasin • Calreticulin • Class II chaperones • Invariant chain • DMA and DMB Outline

4. Humoral and Cell-mediated Immune Responses

5. Types of T cells • Cytotoxic T cells (CTLs) • Kill virally infected cells • Kill cells containing cytosolic bacteria • Kill tumor cells • Inflammatory T cells (TH1) • A. Activate macrophages to kill intracellular bacteria • Helper T cells (TH2) • Activate B cells to make antibody

6. Class I • Heterodimer-2 subunits, a chain and b-2 microglobulin • Binding site formed by a1 and a2 domains • Peptides are 8-9 residues • Antigens derived from endogenous proteins • Are recognized by CD8+ T cells (cytotoxic) • Class II • Heterodimer-a and b chains • Amino-terminal domains of a and b form the antigen • binding site • C. Antigens derived from exogenous antigens • D. Are recognized by CD4+ T cells (helper) • E. Peptides are 12 to >20 amino acids Structural Organization of MHC Molecules

7. MHC Molecules

8. Major Histocompatibility Complex

9. MHC class I and class II Molecules

10. MHC class I (top view)

12. b2-microglobulin MHC class I

13. MHC class II DRb chain

14. Anchor Residues for MHC class I peptides

15. Anchor Residues for MHC class II peptides

16. MHC class I Polymorphisms

17. MHC class I Polymorphisms

19. Antigen Processing and Presentation

20. MHC Restriction(class I) LCM Lymphocytic choriomeningitis

21. Antigen Processing Requirements for Helper T cell Activation

22. Antigen-presenting Cells

23. Cytosolic and Endocytic Pathways

24. Degradation of Intracellular Proteins

25. Transporter associated with Antigen Processing Bare lymphocyte syndrome (BLS)

26. Generation of Peptide-class I MHC Complexes

27. Assembly of MHC class I Molecules

28. Demarcation between MHC class I and class II Processing Pathways

29. Assembly of MHC class II Molecules

30. Study Objectives • Compare and contrast the structures of MHC class I and class II molecules. • How do the peptide binding sites differ between them? • What is the biological function of these molecules? • What is the relationship between MHC molecules and helper and cytotoxic T cell responses? • 5. Compare and contrast class I and class II MHC-restricted • responses with regard to • A. source of antigens • B. antigen processing requirements • C. role of chaperones • D. types of T cell involved • 6. Discuss the invariant chain’s role in the demarcation between class I and class II MHC-restricted responses. • 7. Discuss DMA and DMB’s possible role in antigen processing.