MHC
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MHC. Histocompatibility Ags 1-Minor Histocompatibility Complex HLA 2-Major Histocompatiblity Complex H-2. Major Histocompatibility Complex (MHC). What is MHC? HLA H-2 Minor histocompatibility antigens.

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MHC

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Mhc

MHC

Histocompatibility Ags

1-Minor Histocompatibility Complex

HLA

2-Major Histocompatiblity Complex H-2


Major histocompatibility complex mhc

Major Histocompatibility Complex(MHC)

  • What is MHC?

    • HLA

    • H-2

    • Minor histocompatibility antigens


Significance of the mhc

Significance of the MHC

  • role in immune response

  • role in organ transplantation

  • role in predisposition to disease


Major histocompatibility complex history

Major Histocompatibility Complex: History

  • Transplantation: autograft or autologus(syngraft) no regection allograft or allogenic graft rejection


Genetic barriers to transplantation

Genetic barriers to transplantation

  • autologous: in the same individual

  • isologous: between genetically Identical individuals, i.e., identical twins (inbred animals)

  • homologous: between individuals of the same species

  • heterologous: between individuals different species


The laws of transplantation

The laws of transplantation


The mouse mhc genes

The mouse MHC genes


Mouse mhc

Mouse MHC

  • H-2K H-2 I-A= DP II human

  • H-2D H-2 I-E = DR human

  • H-2L


Hla detection

HLA Detection

  • 1-by serologicaly

  • 2-by mixed leukocyte reaction(MLR)


Mhc

CD4+TH1

CD8+preCTL

CD8+CTL

Cytotoxic T lymphocyte (CTL) generation


The human mhc genes

The human MHC genes


Polymorphism of mhc genes

Polymorphism of MHC genes


Differential expression of mhc antigens

Differential expression of MHC antigens

  • Class-I expressed on all nucleated cells in man, and also on erythrocytes in mice.

  • Class-II expressed primarily on antigen presenting cells (dendritic cells, macrophages and B cells)


Properties mhc

PROPERTIES MHC

  • Immune responses: antibody formation

  • Highly polymorphic

  • Bind peptide: recognized by T cells: Th__MHCII

  • Tc__MHCI

  • Co_dominant

  • Three-dimensional structure determined by X-ray crystallography


Structure of class i mhc

α1

NH2

NH2

Alloantigenic

sites

β2

NH2

α2

COOH

CHO

α3

Disulfide bridge

Papain cleavage

Plasma membrane

OH

P

Cytoplasm

COOH

Structure of Class I MHC


Structure of class i mhc1

Structure of Class I MHC

  • Two polypeptide chains, a long α chain and a short β chain, called β2 microglobulin

  • Four regions:

  • Peptide-binding region - a groove formed from α1 and α2 domains of the α chain :

    8-10 residue,greatest variability,anchor site

    2. Immunoglobulin-like region = highly conserved α3 domain that homologus to Ig domain and non-covalently bound to beta2 Mic- site to which CD8 on T cell binds


Structure of class i mhc continued

Structure of Class I MHC(continued)

  • Transmembrane region – stretch of hydrophobic amino acids spanning membrane

  • Cytoplasmic region – contains sites for phosphorylation and binding to cytoskeletal elements


Structure of class i mhc2

α1

NH2

NH2

Alloantigenic

sites

β2

NH2

α2

COOH

CHO

α3

Disulfide bridge

Papain cleavage

Plasma membrane

OH

P

Cytoplasm

COOH

Structure of Class I MHC


Structure of class i mhc peptide binding region

a “groove” composed of an α-helix on two opposite walls and eight β-pleated sheets forming the floor

residues lining groove most polymorphic

peptide in groove 8-10 amino acids long

specific amino acid on peptide required for “anchor site” in groove

Structure of Class I MHC Peptide-binding Region


Variability for polymorphism

Variability For Polymorphism


Structure of class ii mhc

NH2

NH2

α1

β1

CHO

CHO

α2

β2

CHO

Plasma membrane

Cytoplasm

COOH

COOH

Structure of Class II MHC


Structure of class ii mhc1

Two polypeptide chains, α and β, of roughly equal length.

Four regions:

Peptide-binding region – a groove formed from the α1 and β1 domains of the α and β chains – site of polymorphism

Immunoglobulin-like region – conserved α2 and β2 domains – β2 is site to which CD4 on T cell binds

Structure of Class II MHC


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