Major Histocompatibility Complex (MHC): Mouse

Abstract

The major histocompatibility complex (MHC) of the mouse, which is called the H2 complex, is located on chromosome 17. It contains genes critical to the functioning of the immune system, the products of which are intimately involved in the initiation of immune responses. The proteins made by these genes display a significant amount of polymorphism, or sequence variability. Few genes possess this degree of polymorphism, but it is critical to the immune response and to the survival of a species. The chief characteristic of MHC molecules is their ability to bind small peptides. These bound peptides along with specific areas of the MHC molecule are the structures that interact with the T‐cell receptor (TCR) leading to activation of a T‐cell immune response, which in turn can active other cells of immune system. Thus, they determine which TCRs are functional which in turn indicates which peptides a T cell will respond to.

Key Concepts

  • The historical background and the genetics of MHC development are described.
  • The expression and function of MHC class I genes is described.
  • MHC class I molecules are expressed on virtually all nucleated cells and function to present foreign and self‐antigens to the immune system.
  • MHC class I expression is dependent on peptide binding in the peptide binding groove of the molecule.
  • MHC class I polymorphism is important for species resistance to infectious disease.
  • The expression and function of MHC class II genes is described.
  • MHC class II expression is required for generation and function of CD4 T cells.
  • Nonclassical class I molecules bind a variety of peptide and nonpeptide antigens that are commonly expressed by pathogenic organisms. .
  • The function of other genes found within the H2 complex is described.

Keywords: H2 complex; MHC; MHC restriction; class I; class II; MHC peptide association; T‐cell activation

Figure 1. A map of the H2 complex. Individual loci are identified by location and whether they belong to classes I, II or III. Their grouping within the K, I, S, D and Q/T/M regions is indicated. LMP, lymphocyte membrane protein; TAP, transporter associated with antigen processing and TNF, tumour necrosis factor.
Figure 2. H2 class I and II molecules on the cell surface. The intracellular transmembrane and external domains are identified, as in β2‐microglobulin.
Figure 3. Peptide presentation by class I and II molecules. The peptide fragment is nestled into the groove formed between the two long helical segments. Owing to differences in the structure of peptide binding groove, peptides binding to class I molecules are typically 8–10 amino acids in length while peptides binding to class II can be up to 30 amino acids in length, though most peptides are 13–22 amino acids (Sercarz and Maverakis, ). MHC, major histocompatibility complex.
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Further Reading

Abbas AK, Lichtman AH and Pillai S (2015) Cellular and Molecular Immunology, 8th edn. Philadelphia: Saunders.

Mak TW, Saunders ME and Jett BD (2014) Primer to the Immune Response, 2nd edn. Cambridge: Elsevier.

Murphy KM (2011) Janeway's Immunobiology, 8th edn. New York: Garland Publishing.

Painter CA and Stern LJ (2012) Conformational variation in structures of classical and non‐classical MHCII proteins and functional implications. Immunological Reviews 250: 144–157.

Paul WE (2012) Fundamental Immunology, 7th edn. Philadelphia: Lippincott Williams and Wilkins.

Salio M, Silk JD, Jones EY and Cerundolo V (2014) Biology of CD1 and MR1‐restricted T cells. Annual Review of Immunology 32: 323–366.

Zhu J, Yamane H and Paul WE (2010) Differentiation of effector CD4 T cell populations (*). Annual Review of Immunology 28: 445–489.

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Stuart, Patrick M(Jun 2015) Major Histocompatibility Complex (MHC): Mouse. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000921.pub4]