Major Histocompatibility Complex (MHC): Mouse

Patrick M Stuart, Saint Louis University, Missouri, USA

Published online: September 2010

DOI: 10.1002/9780470015902.a0000921.pub3

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 TCR's 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.
  • The function of CD8+ T cells requires expression of MHC class I genes.
  • Peptide loading is required for MHC class I expression.
  • 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 are important in generating responses to commonly expressed molecules 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 2-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, 2003). MHC, major histocompatibility complex.
Figure 4. Helper T-cell differentiation. (a) The classical monolithic view: lineages and master regulators. Initial studies arising from in vitro cultured TH1 and TH2 cells led to the idea that these subsets behaved like lineages, meaning that their phenotype (i.e. selective cytokine production) was inflexible. Accordingly, these subsets expressed lineage-defining transcription factors that were sufficient to impart this selective cytokine production. As newer subsets of cytokine-producing cells were identified, they too were viewed as stable lineages. (b) Flexibility and plasticity of helper T cells. Recent studies of TH cells have revealed more flexibility in cytokine production than predicted by earlier work, and there are now many examples of plasticity of TH cell phenotype. CD4+ T cells can change their profile of cytokine production, and there are now circumstances in which the expression of master regulators is transient or instances where cells express more than one master regulator. Reprinted with permission from O'Shea and Paul (2010).
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 Further Reading
    book Abbas AK, Lichtman AH and Pillai S (2010) Cellular and Molecular Immunology, 7th edn. Philadelphia: Saunders.
    book Janeway CA Jr, Murphy KM, Travers P and Walport M (2007) Immunobiology: The Immune System in Health and Disease, 7th edn. New York: Garland Publishing.
    book Mak TW and Saunders ME (2008) Primer to the Immune Response. Burlington: Academic Press.
    book Paul WE (2008) Fundamental Immunology, 6th edn. Philadelphia: Lippincott Williams and Wilkins.
    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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Article Title: Major Histocompatibility Complex (MHC): Mouse
 
How to Cite close
Stuart, Patrick M(Sep 2010) Major Histocompatibility Complex (MHC): Mouse. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000921.pub3]