The Murine T Cell Antigen Receptor and Associated Structures

The immunochemical approach described in this review has led to the identification of a new component of the T cell surface, the disulfide-linked heterodimer, which has many of the properties expected of a molecule with antigen-specific receptor activity: 1) Expression of the heterodimer is restricted to T cells. 2) The molecule expresses clonotypic epitopes presumably related to the specific antigen recognition site, as well as crossreactive epitopes associated with the molecular framework. 3) At the primary sequence level, the molecule has regions of constant as well as variable structure. The numerous observations from other laboratories that clonotypic antibodies which inhibit antigen-specific reactions are directed against similar disulfide-linked heterodimers provide compelling evidence that this structure is in fact the T cell antigen receptor. Two important conclusions can be drawn from the results of peptide analysis of the receptor subunits. First, the molecular fingerprints of the alpha and beta chains are very different, indicating that the subunits are encoded by different genes. Second, both subunits have constant and variable regions, suggesting that both subunits play a role in producing the antigen combining site. A crucial question that remains to be answered is whether the same or different combining sites are responsible for recognition of antigen and the MHC restricting element. The recent report by Marrack et al. (1983b) that the receptors of two independent T cell hybridomas with the same antigen and MHC specificities expressed the same clonotypic determinant and yielded identical peptide maps (Kappler et al. 1983) provides strong evidence that the heterodimer is responsible for both antigen and MHC recognition. If this is the case, it remains to be determined whether a single site contributed by both subunits recognizes antigen and MHC, or whether one subunit contributes a site for MHC recognition and the other a site for antigen recognition. If, however, as Parham (1984) has recently proposed, conserved rather than polymorphic regions of the MHC product are recognized in MHC restriction, it is possible that the heterodimer functions solely in recognition of antigen, and the restriction may be provided by accessory proteins in a receptor complex. Definitive conclusions as to the role of the individual chains will probably require construction of functional T cells using molecular clones of the genes encoding the receptor and accessory proteins. Recently, the molecular cloning of cDNA encoding putative T cell receptors has been reported from murine (Hedrick et al. 1984) and human (Yanagi et al. 1984) cells.(ABSTRACT TRUNCATED AT 400 WORDS)