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Major Histocompatibility Complex. Human Scent . MHC. Found on Chromosome 6 A set of genes with immunological and non-immunological functions Prevents inbreeding in humans Influences mate selection Used for peptide binding and presentation to T lymphocytes. MHC Structure. 6p21.31
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Major Histocompatibility Complex Human Scent
MHC • Found on Chromosome 6 • A set of genes with immunological and non-immunological functions • Prevents inbreeding in humans • Influences mate selection • Used for peptide binding and presentation to T lymphocytes
MHC Structure • 6p21.31 • 3.6Mbp • The HLA complex is divided into three regions: class I, II, and III regions • The classical HLA antigens encoded in each region are HLA-A, -B, and -C in the class I region • All class I genes are between 3 and 6 kb • HLA-DR, -DQ and -DP in the class II region • class II genes are 4-11 kb long
MHC Expression • Co-dominant expression • Both alleles contribute to the phenotype equally • The co-dominant expression and haplotypical transmission have an important consequence: within a family • HLA-identical sibling frequency should be 25%
Polymorphism • MHC has the greatest degree of polymorphism in the human genome • Histocompatibility molecules are glycoproteins expressed at the surface of almost all vertebrate cells. • They get their name because they are responsible for the compatibility — or rather the lack of it — of the tissues of genetically different individuals. • Monozygotic ("identical") human twins have the same histocompatibility molecules on their cells, and they can accept transplants of tissue from each other.
Class I • Class I molecules are composed of two polypeptide chains • The MHC-encoded polypeptide is about 350 amino acids long and glycosylated, • Total molecular weight of about 45 kDa • This polypeptide folds into three separate domains called alpha-1, alpha-2 and alpha-3 • ß2-microglobulin is a 12 kDa polypeptide that is non-covalently associated with the alpha-3 domain
MHC Protein • Between the alpha-1 and alpha-2 domains lies a region bounded by a beta-pleated sheet on the bottom and two alpha helices on the sides • This region is capable of binding (via non-covalent interactions) a small peptide of about 10 amino acids
Class II • Class II molecules are composed of two polypeptide chains, both encoded by the D region. • These polypeptides (alpha and beta) are about 230 and 240 amino acids long, respectively, and are glycosylated • Molecular weights of about 33 kDa and 28 kDa. • These polypeptides fold into two separate domains; alpha-1 and alpha-2 for the alpha polypeptide, and beta-1 and beta-2 for the beta polypeptide.
Class II • Between the alpha-1 and beta-1 domains lies a region very similar to that seen on the class I molecule. • This region, bounded by a beta-pleated sheet on the bottom and two alpha helices on the sides • Capable of binding (via non-covalent interactions) a small peptide of about 10 amino acids
Class I vs. Class II • First, class I molecules are found on virtually every cell in the human body. • Class II molecules, in contrast, are only found on B-cells, macrophages and other "antigen-presenting cells" (APCs)
