The Major Histocompatibility Molecules Bind Antigenic Peptides

The major histocompatibility complex (MHC) is a large genetic complex with multiple loci. The MHC loci encode two major classes of membrane-bound glycoproteins: class Iand class II MHC molecules.As noted above, T_H cells generally recognize antigen combined with class II molecules, whereas T_C cells generally recognize antigen combined with class I molecules.

MHC molecules function as antigen-recognition molecules, but they do not possess the fine specificity for antigen characteristic of antibodies and T-cell receptors. Rather, each MHC molecule can bind to a spectrum of antigenic peptides derived from the intracellular degradation of antigen molecules. In both class I and class II MHC molecules the distal regions (farthest from the membrane) of different alleles display wide variation in their amino acid sequences. These variable regions form a cleft within which the antigenic peptide sits and is presented to T lymphocytes (see Figure 5).

Different allelic forms of the genes encoding class I and class II molecules confer different structures on the antigen-binding cleft with different specificity. Thus the ability to present an antigen to T lymphocytes is influenced by the particular set of alleles that an individual inherits.

Figure 5. The role of MHC molecules in antigen recognition by T cells. (a) Class I MHC molecules are expressed on nearly all nucleated cells. Class II MHC molecules are expressed only on antigenpresenting cells. T cells that recognize only antigenic peptides displayed with a class II MHC molecule generally function as T helper (T_H) cells. T cells that recognize only antigenic peptides displayed with a class I MHC molecule generally function as T cytotoxic (T_C) cells. (b) This scanning electron micrograph reveals numerous T lymphocytes interacting with a single macrophage. The macrophage presents processed antigen combined with class II MHC molecules to the T cells. [Photograph from W. E. Paul (ed.), 1991, Immunology: Recognition and Response, W. H. Freeman and Company, New York; micrograph courtesy of M. H. Nielsen and O. Werdelin.]