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

FUNCTION OF MHC MOLECULE(s)

Presentation of antigens to T lymphocytes

MHC

H-2

RT-1 SLA

GPLA

FLA

DLA

HLA

Human Leukocyte Antigens

BASIC FEATURES of MHC

polygenicity (> 200 genes)

polymorfism (genes within species have alternative variants – alleles)

George SnellJean Dausset

Baruj Benacerraf1980

Stucture of class I and class II MHC molecules

Cleft ofCleft of MHC MHC

Anchoring amino acids

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

MHC II MHC I

TCR TCRCD4 CD8

CD4+ T cell(helper)

A P C A P C

CD8+ T cell(cytotoxic)

Peter C. Doherty

Rolf M. Zinkernagel

1996

Figure 5-12Nomenklature and genetic organization of HLA

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

chr. 6

Regions: II III IHLA-B

HLA-C

HLA-A

HLA

HLA-B HLA-C HLA-A

HLA-B

HLA-C

HLA-A

genes

cellmembrane

chromosome

molecules

chr. 6

Regions II III I

DPB

DPA

DQB

DQA

DRB

DRA

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

Figure 5-14 part 1 of 2

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

Features of antigens recognized by T lymphocytes

1.Peptide 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 I pathway

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"

MHC class II pathway

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