A model for T cell receptor and MHC/peptide interaction.

For some time it has been known that T cell recognition of antigen occurs in an MHC restricted fashion (1–3). Much recent evidence suggests that the antigens ‘seen’ by T cell receptors (TcR) are fragments (presumably derived by intracellular processing) bound to MHC molecules at a single site (4–10) By contrast, the immunoglobulin (Ig) B cell receptor can bind to native antigen alone. Structurally and genetically however, both immunoglobulins and T cell receptors seem very similar. Both are derived from the relatively random juxtaposition of different coding segments (V, D and J) of DNA to produce proteins that differ in their N-terminal domains (V-domains), but are the same elsewhere (C domains) (11–13). Ig V region domains from the heavy and light chain polypeptides (VH and VL) pair to form the ligand binding region (14). By analogy, it seems likely that the binding site for antigen and MHC is formed by pairs of TcR V-domains (either α:β or γ: δ). In the Ig variable regions, sequence diversity is concentrated in three distinct ‘hypervariable regions’(15, 16). These amino acids form the principal points of contact with antigens and are thus referred to as complementarity determining regions (CDR’s) (17, 18).