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

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


Significance of the MHC

  • role in immune response

  • role in organ transplantation

  • role in predisposition to disease


Major Histocompatibility Complex: History

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


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 mouse MHC genes


Mouse MHC

  • H-2K H-2 I-A= DP II human

  • H-2D H-2 I-E = DR human

  • H-2L


HLA Detection

  • 1-by serologicaly

  • 2-by mixed leukocyte reaction(MLR)


CD4+TH1

CD8+preCTL

CD8+CTL

Cytotoxic T lymphocyte (CTL) generation


The human MHC genes


Polymorphism of MHC genes


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

  • 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


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

  • 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)

  • Transmembrane region – stretch of hydrophobic amino acids spanning membrane

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


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


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


NH2

NH2

α1

β1

CHO

CHO

α2

β2

CHO

Plasma membrane

Cytoplasm

COOH

COOH

Structure of Class II MHC


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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