Themes > Science > Life Sciences > General Biology > Immunology > Recognition Systems in Immunity > The Major Histocompatibility Complex > Biological role of the MHC

The products of the MHC play a fundamental role in regulating immune responses. T cells must recognise antigen as a complex with MHC molecules. This requires antigen to be processed by unfolding and proteolytic digestion before it complexes with the MHC molecule. Once formed the complex of antigenic peptide and MHC are generally very stable (half life ~ 24hrs). Thus the biological role of MHC proteins is to bind small peptides and to "present" these at the cell surface for the inspection of T cell antigen receptors. The allelic variation of MHC molecules is functionally reflected in the selection of peptides which can bind, each allelic product has a unique set of peptides which it can bind with high affinity (though rarely particular peptides may bind to more than one MHC allele).

In a normal animal or cell the majority of MHC molecules will be complexed with self peptides, "empty" MHC molecules are less stable especially in the case of class I products.

Summary of Peptide Binding to MHC

  • There are 50,000 - 100,000 MHC molecules on a typical cell
  • Most 'normal' MHC molecules are occupied by self peptides
  • The requirements for binding to a particular allele are met by ~1/1000 - 1/10000 random peptides
    Click here to see some examples of allele specific sequence motifs
  • This stringency has to make a balance between allowing too many peptides to bind
    - this would lead to the population of any given MHC allele on a single cell displaying a very large number of peptides each at only a few copies per cell

    and restricting binding to tightly
    - this would make it easier for small pathogens to escape the immune response by having no peptides which bind to a given host's MHC molecules.
  • The typical population of ~100,000 MHC class I molecules of a single allotype on a normal cell displays >1000 different peptides
  • Individual peptide-MHC complexes are represented in widely different amounts from 1 - 5000 molecules/cell (mean~100)
  • T cells vary in the threshold for activation from a few (1?) complexes/cell to a few thousand, depending on the affinity, activation state etc. of the T cell and on the antigen presenting cell.

Added Value

Selection of T cells during thymic development ensures deletion of clones recognising self MHC/self peptide complexes with high affinity and survival/maturation of only those clones which recognise these self complexes with moderate affinity. The requirement to recognise self MHC complexes with moderate affinity means that MHC alleles determine the immune response phenotype of the individual by selecting the mature T cell repertoire.

Go to lecture 9 for further details about thymic selection


Information provided by: http://www-immuno.path.cam.ac.uk