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MHC I, II, Ag-Presentation Kuby, Immunology , 5 th Edition Chapters 7 and 8. Jim Collawn MCLM 350 jcollawn@uab.edu. Study Objectives. Compare and contrast the structures of MHC class I and class II molecules. How do the peptide binding sites differ between them?
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MHC I, II, Ag-PresentationKuby, Immunology, 5th EditionChapters 7 and 8 Jim Collawn MCLM 350 jcollawn@uab.edu
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.
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
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
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
b2-microglobulin MHC class I
MHC class II DRb chain
MHC Restriction(class I) LCM Lymphocytic choriomeningitis
Antigen Processing Requirements for Helper T cell Activation
Transporter associated with Antigen Processing Bare lymphocyte syndrome (BLS)
Demarcation between MHC class I and class II Processing Pathways
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.