Correlation of T cell receptor V beta gene family with MHC restriction

Antigen-specific T cells recognize antigen in association with class I or class II products of the MHC. T cell activation results from the formation of a ternary complex involving nominal antigen, the appropriate MHC molecule, and the TCR. Studies of the genetic structure of the TCR a and # chains have not provided a mechanism for the corecognition of antigen and MHC by the TCR (1). Research on this problem has therefore focused on two main areas; the specificity of the interaction between MHC molecules and nominal antigen, and the analysis of T cell receptors specific for well-defined epitopes . The interaction between MHC molecules and nominal antigen has been demonstrated experimentally (2-4), but the structure/function relationship of the a and 0 chains of the TCR within the ternary complex has not yet been elucidated . One possibility is that one chain of the TCR is primarily responsible for binding to the MHC restricting molecule, while the other confers specificity for nominal antigen . The simplest version of this model, in which TCR a and ,8 chains from T cells of unrelated specificity would be independently assorted to produce new MHC/antigen specificities, has been disproved by Kappler et al . (5). However, there is some evidence from the cytochrome c system that TCR a and (3 chains may be involved in the recognition of antigen and MHC, respectively . Fink et al . (6) have suggested that changes in the TCR ,Q chain appear to alter the MHC restriction of some cytochrome c-reactive T cell hybridomas . More recently, Winoto et al . (7) indicated that a particular TCR a chain was expressed in the majority of cytochrome c-specific T cell lines, regardless of the strain of origin of these lines, and suggested that there was a correlation between TCR a chain usage and antigen recognition. We have recently generated a series of T cell clones from individual DBA/2 mice, specific for sperm whale myoglobin (SpW Mb), the antigen fine specificity of which has been extensively characterized using synthetic peptides .' , ' We have studied this panel of T cell clones for their TCR ,Q chain usage by FACS analysis using mAbs specific for a particular family of TCR V#chain genes.