1. 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

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

3. H-2
GPLA
DLA
MHC
FLA
RT-1
SLA

4. Human Leukocyte Antigens
HLA
Human Leukocyte Antigens

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

6. George Snell
Jean Dausset
Baruj Benacerraf
1980

7. Stucture of class I and class II MHC molecules

12. Cleft of MHC
Anchoring amino acids

14. 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

15. 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

16. Peter C. Doherty
Rolf M. Zinkernagel
1996

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

18. 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

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

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

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

22. 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

25. Figure 5-14 part 1 of 2

33. 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

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

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

36. 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

40. MHC class I pathway

44. The Nobel Prize in Chemistry 2004
"for the discovery of ubiquitin-mediated protein degradation"
                          
Aaron Ciechanover
Avram Hershko
Irwin Rose
    1/3 of the prize
Israel
USA
Technion – Israel Institute of Technology Haifa, Israel
University of California Irvine, CA, USA
b. 1947
b (in Karcag, Hungary)
b. 1926

45. MHC class II pathway

48. 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