Site-directed mutations in the VDJ junctional region of a T cell receptor beta chain cause changes in antigenic peptide recognition

In order to assess the importance of a conserved amino acid in the VDJ junctional region of the beta chain of T cell receptors (TCRs) specific for pigeon cytochrome c, we generated T cell transfectant clones that express either a TCR identical to that of the cytochrome c-specific clone D6 or a mutated form of the D6 TCR, in which the conserved residue was replaced by one of two other amino acids. We have found that one substitution alters antigen fine specificity, while the other substitution abolishes all detectable cytochrome c response. On the basis of these findings, we propose that this conserved amino acid is a key residue in determining the antigen specificity of the D6 TCR.