Download - M AJOR H ISTOCOMPATIBILITY C OMPLEX
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MAJOR HISTOCOMPATIBILITY COMPLEX
MHC
definition and basic features
structure of MHC class I and II molecules
structure and organization of MHC genes
inheritance and expression of MHC genes
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FUNCTION OF MHC MOLECULE(s)
Presentation of antigens to T lymphocytes
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MHC
H-2
RT-1 SLA
GPLA
FLA
DLA
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HLA
Human Leukocyte Antigens
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BASIC FEATURES of MHC
polygenicity (> 200 genes)
polymorfism (genes within species have alternative variants – alleles)
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George SnellJean Dausset
Baruj Benacerraf1980
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Stucture of class I and class II MHC molecules
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Cleft ofCleft of MHC MHC
Anchoring amino acids
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DP
DQ
DR
ALL NUCLEATED CELLS DENDRITIC CELLS MACROFAGESB CELLS
MHC class I MHC class II
2m
2m
2m
A
B
C
TISSUE DISTRIBUTION AND NOMENCLATURE OF MHC
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MHC II MHC I
TCR TCRCD4 CD8
CD4+ T cell(helper)
A P C A P C
CD8+ T cell(cytotoxic)
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Peter C. Doherty
Rolf M. Zinkernagel
1996
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Figure 5-12Nomenklature and genetic organization of HLA
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centromere telomere
GB C E A FAB A B A B
TNFC4B C4A Bf C2DP DQ DR
II class III class I class
6. chromosome
HLA
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chr. 6
Regions: II III IHLA-B
HLA-C
HLA-A
HLA
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HLA-B HLA-C HLA-A
HLA-B
HLA-C
HLA-A
genes
cellmembrane
chromosome
molecules
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chr. 6
Regions II III I
DPB
DPA
DQB
DQA
DRB
DRA
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DPB
DPA
DQB
DQA
DRB
DRA
DP
beta
DP
alf
a
DQ
beta
DQ
alf
a
DQ molecule
DR
beta
DR
alf
a
DR molecule
DP molecule
genes
cellmembrane
chromosome
molecules
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Figure 5-14 part 1 of 2
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PROCESSING AND PRESENTATION OF PROTEIN ANTIGENS
Antigen processingpeptide derivation out of native proteins
Antigen presentationDisplaying peptides in complex with self MHC on the cell surface
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Features of antigens recognized by T lymphocytes
1.Peptide antigens
2. Linear determinantes
3. On the cell surface within own MHC
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Two pathways of antigen processing and presentation
MHC class I pathway
MHC class II pathway
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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
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MHC class I pathway
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The Nobel Prize in Chemistry 2004
Aaron Ciechanover
Avram Hershko
Irwin Rose
1/3 of the prize 1/3 of the prize 1/3 of the prize
Israel Israel USA
Technion – Israel Institute of Technology Haifa, Israel
Technion – Israel Institute of Technology Haifa, Israel
University of California Irvine, CA, USA
b. 1947 b. 1937(in Karcag, Hungary)
b. 1926
"for the discovery of ubiquitin-mediated protein degradation"
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MHC class II pathway
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HLA-DR, HLA-DP, HLA-DQj.MHC class II molecules are expressed on10.
proteasomei.MHC class I molecules are expressed on9.
all nucleated cellsh.MHC class II presents the peptides to8.
recognition by T lymphocytesg.MHC class I presents the peptides to7.
MHC class IIf.Peptides derived from endogenous proteins that form the complex with MHC class I are formed in
6.
dendritic cells, macrophages and B lymphocytes
e.Endogenously synthesized (within the cell) antigens are presented in
5.
CD4+ T-lymphocytesd.Exogenous antigens that enter the cell by endocytosis are presented within
4.
HLA-A, HLA-B, HLA-Cc.Processing and presentation of antigens is necessary for
3.
CD8+ T-lymphocytesb.Human MHC class II molecules are2.
MHC class Ia.Human MHC class I molecules are1.
10.____9.____8.____7.____6.____5.____4.____3.____2.____1.____c j g f a i b d h e