Ch. 8. The Major Histocompatibility Complex and Antigen Presentation

1. Ch. 8. The Major Histocompatibility Complex and Antigen Presentation Generation of T cell responses Antigen processing and presentation Development of T and B cells Control of B cell response by T cells Cell-mediated immunity Ch. 8

2. T cell antigens are processed and presented by MHC molecules (p. 82) Ch. 8

3. All mammalian species have a MHC major histocompatibility complex tightly linked cluster of genes gene products are cell-surface proteins involved in cell-cell interaction antigen presentation recognition of self-nonself molecules Humans- HLA complex (human leukocyte antigen) Mice- H-2 Ch. 8

4. Three classes of MHC molecules Class I- almost all nucleated cells antigen presentation to cytotoxic T cells Class II- on antigen-presenting cells antigen presentation to helper T cells These molecules are cell-surface glycoproteins Class III- secreted proteins complement components inflammation Ch. 8

5. Organization of the MHC (p. 190) Ch. 8

6. Each locus is polymorphic Each set of alleles on one chromosome is called a haplotype They are expressed codominantly: you get one haplotype from each parent both are expressed on the cell surface (All nucleated cells express MHC Class I) APCs express both Class I and Class II Ch. 8

7. Skin graft acceptance is controlled by MHC p. 176 p. 192 Ch. 8

8. Ch. 8

9. p. 192 Ch. 8

10. A widely used experimental system is mouse strains Syngeneic strains- identical at all (H-2) loci (e.g., BALB/c, DBA/2, NZB) Congenic- identical except at a single locus Strains were produced with careful breeding over many generations Ch. 8

11. What do the MHC molecules look like? p. 194 Class II Class I Ch. 8

12. Three-dimensional structure of human Class I p. 195 p. 195 Ch. 8

13. MHC molecules bind peptides. Binding sites and the nature of the peptides is slightly different. p. 197 Ch. 8

14. MHC molecules are very polymorphic Not due to gene rearrangement, like B and T cells but multiple alleles. Alleles vary quite a bit. Since there is so much polymorphism at each of the several loci, the theoretical degree of diversity is huge. Ch. 8

15. Significance of polymorphism? Immune responsiveness is determined by MHC Class II haplotype (“MHC restriction”) Ch. 8

16. Possible explanations • Different MHC class II molecules differ in their • ability to bind antigen 2. T cells may not recognize certain MHC- peptide combinations, because they resemble self-antigen too closely. These “forbidden clones” were eliminated during development, resulting in a “hole in the repertoire.” Ch. 8

17. From Kuby, 5th edition Ch. 8

18. Linkage disequilibium: an association between some MHC alleles and some diseases Complex interaction between genes and the environment (e.g., ID twins) May result from altered Ag presentation or lack of TCR’s to recognize processed Ag Some MHC molecules may mimic receptors for pathogens or their toxins Reduction in polymorphism may predispose species toward disease (e.g., cheetahs) Ch. 8