MAJOR HISTOCOMPATIBILITY COMPLEX MHC MAJOR HISTOCOMPATIBILITY COMPLEX definition and basic features structure of MHC class I and II molecules structure and organization of MHC genes inheritance and expression of MHC genes

FUNCTION OF MHC MOLECULE(s) Presentation of antigens to T lymphocytes

H-2 GPLA DLA MHC FLA RT-1 SLA

Human Leukocyte Antigens HLA Human Leukocyte Antigens

polygenicity (> 200 genes) polymorfism (genes within species have BASIC FEATURES of MHC polygenicity (> 200 genes) polymorfism (genes within species have alternative variants – alleles)

George Snell Jean Dausset Baruj Benacerraf 1980

Stucture of class I and class II MHC molecules

TISSUE DISTRIBUTION AND NOMENCLATURE OF MHC ALL NUCLEATED CELLS DENDRITIC CELLS MACROFAGES B CELLS a b2m A B C a b DP DQ DR MHC class I MHC class II

CD4+ T cell CD8+ T cell A P C A P C TCR TCR CD4 CD8 MHC II MHC I (helper) CD8+ T cell (cytotoxic) TCR TCR CD4 CD8 MHC II MHC I A P C A P C

Peter C. Doherty Rolf M. Zinkernagel 1996

Nomenklature and genetic organization of HLA Figure 5-12 Nomenklature and genetic organization of HLA

HLA 6. chromosome DP DQ DR TNF B C E A F G centromere telomere C4B C4A Bf C2 B A B A B A B C E A F G II class III class I class

HLA chr. 6 Regions: II III I HLA-B HLA-C HLA-A

molecules HLA-C HLA-A HLA-B cell membrane HLA-B HLA-C HLA-A chromosome genes

chr. 6 Regions II III I DPB DPA DQB DQA DRB DRA

molecules DQ beta DP beta DQ alfa DR beta DP alfa DR alfa cell membrane DP molecule DPB DPA DQB DQA DRB DRA chromosome genes

Figure 5-14 part 1 of 2

PROCESSING AND PRESENTATION OF PROTEIN ANTIGENS Antigen processing peptide derivation out of native proteins Antigen presentation Displaying peptides in complex with self MHC on the cell surface

Features of antigens recognized by T lymphocytes Protein antigens 2. Linear determinantes 3. On the cell surface within own MHC

Two pathways of antigen processing and presentation MHC class I pathway MHC class II pathway

COMMON FEATURES OF BOTH PATHWAY OF ANTIGEN PROCESSING AND PRESENTATION peptide antigens are formed by proteolytic cleavage in the APC’s organelles peptide binding to MHC occurs before they appear on the cell surface organelles and enzymes of general protein metabolism are used no distinction of foreign from self proteins

MHC class II pathway

1. Human MHC class I molecules are a. MHC class I 2. Human MHC class II molecules are b. CD8+ T-lymphocytes 3. Processing and presentation of antigens is necessary for c. HLA-A, HLA-B, HLA-C 4. Exogenous antigens that enter the cell by endocytosis are presented within d. CD4+ T-lymphocytes 5. Endogenously synthesized (within the cell) antigens are presented in e. dendritic cells, macrophages and B lymphocytes 6. Peptides derived from endogenous proteins that form the complex with MHC class I are formed in f. MHC class II 7. MHC class I presents the peptides to g. recognition by T lymphocytes 8. MHC class II presents the peptides to h. all nucleated cells 9. MHC class I molecules are expressed on i. proteasome 10. MHC class II molecules are expressed on j. HLA-DR, HLA-DP, HLA-DQ 1.____ c 2.____ j 3.____ g 4.____ f 5.____ a 6.____ i 7.____ b 8.____ d 9.____ h 10.____ e