The MHC encodes two types of glycoproteins essential for immune recognition, commonly called class I and class II MHC molecules. A comparison of the genetic maps of the mouse and human MHCs shows the presence of several class I MHC genes and several class II MHC genes, even though their arrangement shows variation between the two species (see Figure 23-21). In addition to the class I and class II MHC molecules, the MHC encodes key components of the antigen-processing (e.g., proteolysis) and presentation machinery. Finally, the typical vertebrate MHC also encodes components of the complement cascade.

Both class I and class II MHC proteins are involved in presenting antigen to T cells, but they serve two broadly distinct functions. Class I MHC products present antigens to cytotoxic T cells, licensing them to destroy infected cells. Cytotoxic T cells use class I MHC molecules as their principal restriction elements. These T cells are characterized by the expression of CD8, a surface glycoprotein that determines the ability of the T cells that carry it to interact with class I MHC products. Most, if not all, nucleated cells constitutively express class I MHC molecules, and many can support replication of viruses. Cytotoxic T cells then recognize and kill the infected cells via surface-displayed class I MHC molecules that display virus-derived antigen (peptide).

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Class II MHC products are found exclusively on specialized antigen-presenting cells, also called professional APCs. These APCs present antigens via class II MHC molecules to a class of T lymphocytes called helper T cells. This presentation is the start of an adaptive immune response that also enables cytotoxic T cells to kill their targets and assists B cells in producing antigen-specific antibodies. B cells cannot undergo final differentiation into antibody-secreting plasma cells without assistance from helper T cells. Helper T cells express a surface glycoprotein called CD4 and use class II MHC molecules as restriction elements. The constitutive expression of class II MHC molecules is confined to professional APCs, which include B cells, dendritic cells, and macrophages. (Several other cell types, such as some epithelia, can be induced to express class II MHC molecules under specific circumstances, but we will not discuss them.) Again, the underlying cell biology that describes the expression, assembly, and mode of antigen presentation by class II MHC molecules fits this functional specialization rather neatly, as we shall see below.

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The two major groups of functionally distinct T lymphocytes—cytotoxic T cells and helper T cells—can thus be distinguished by the unique profile of membrane proteins displayed at the cell surface and by the MHC molecules they use as restriction elements:

Both CD4 and CD8, along with many other proteins of the immune system, including the B-cell and T-cell receptors and the polymeric IgA receptor, belong to the immunoglobulin (Ig) superfamily of proteins, all of which have one or more Ig domains. The molecular basis for the strict correlation between expression of CD8 and use of class I MHC molecules as the restriction element, or between expression of CD4 and use of class II MHC molecules as the restriction element, will become evident once the structure and mode of action of MHC molecules has been described.