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

13. 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

14. 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

15. Peter C. Doherty
Rolf M. Zinkernagel
1996

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

17. 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

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

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

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

21. 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

24. Figure 5-14 part 1 of 2

32. 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

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

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

35. 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

42. MHC class II pathway

44. 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