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MHC

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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  1. MHC Histocompatibility Ags 1-Minor Histocompatibility Complex HLA 2-Major Histocompatiblity Complex H-2

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

  3. Significance of the MHC • role in immune response • role in organ transplantation • role in predisposition to disease

  4. Major Histocompatibility Complex: History • Transplantation: autograft or autologus(syngraft) no regection allograft or allogenic graft rejection

  5. 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

  6. The laws of transplantation

  7. The mouse MHC genes

  8. Mouse MHC • H-2K H-2 I-A= DP II human • H-2D H-2 I-E = DR human • H-2L

  9. HLA Detection • 1-by serologicaly • 2-by mixed leukocyte reaction(MLR)

  10. CD4+TH1 CD8+preCTL CD8+CTL Cytotoxic T lymphocyte (CTL) generation

  11. The human MHC genes

  12. Polymorphism of MHC genes

  13. 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)

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Variability For Polymorphism

  21. NH2 NH2 α1 β1 CHO CHO α2 β2 CHO Plasma membrane Cytoplasm COOH COOH Structure of Class II MHC

  22. 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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