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Major Histocompatibility Complex (MHC)

Major Histocompatibility Complex (MHC)

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    Major Histocompatibility Complex (MHC) Background

    The major histocompatibility complex (MHC) is a large cluster of genes found in most vertebrates. The proteins encoded by the major histocompatibility complex are expressed on the cell surface, and are responsible for lymphocyte recognition and "antigen presentation". The MHC molecules control the immune response through recognition of "self" and "non-self" antigens and, displaying the antigens to T cells that have the capacity to kill or co-ordinate the killing of pathogens and infected or malfunctioning cells. In humans, the 3.6-Mb (3 600 000 base pairs) major histocompatibility complex region on the short arm of chromosome 6 contains 140 genes between flanking genetic markers MOG and COL11A2. About half have known immune functions. The diversity of MHC is important in the immune diversity in the population.

    Traditionally, the major histocompatibility complex is divided into the class I, II and III regions, each containing groups of genes with related functions. Class I molecules are encoded by the BCA region while class II molecules are encoded by the D region. A region between these two on chromosome 6 encodes class III molecules, including some complement components. Class I MHC proteins are found on virtually all cell types. They are composed of two polypeptide chains, a long α chain and a short β chain called β2-microglobulin. Their job is to present antigen fragments to cytotoxic T-cells via the CD8 receptor on the cytotoxic T-cells. The peptide antigens presented in this manner are checked by killer T-cells, which have receptors for the class I MHC proteins. The purpose of this surveillance system is to identify abnormal body cells, and attack and destroy them. Class II MHC proteins are found only on immune cells, specifically on antigen-presenting cells. They are composed of two polypeptide chains an α and a β chain of approximately equal length. Class II MHC molecules present antigen fragments to T-helper cells through via the CD4 receptor on the T-helper cells. Class III has a function very different from that of class I and class II. Class III MHC genes encode several components of the complement system, cytokines, and a collection of many other soluble proteins found in the blood that targets foreign cells and breaks open their membranes.

    Major Histocompatibility Complex (MHC) References

      1. MHC Sequencing Consortium (1999) Complete sequence and gene map of a human major histocompatibility complex. Nature 401: 921-23.
      2. Danchin E, et al. (2004) The major histocompatibility complex origin. Immunol Rev. 98:216-32.
      3. Nagaraju K. (2005) Role of major histocompatibility complex class I molecules in autoimmune myositis. Curr Opin Rheumatol. 17(6):725-30.
      4. Vollers SS, et al. (2008) Class II major histocompatibility complex tetramer staining: progress, problems, and prospects. Immunology. 123(3):305-13.
      5. Vandiedonck C, et al. (2009) The human Major Histocompatibility Complex as a paradigm in genomics research. Brief Funct Genomic Proteomic. 8(5):379-94.