Antigen contact sites in class I major histocompatibility complex-restricted, trinitrophenyl-specific T cell receptors

Abstract

Cloned trinitrophenyl (TNP)-specific cytotoxic T cells (CTL) were obtained from mice transgenic for the beta chain of the antigen-specific receptor (TcR) of a Kb-restricted, TNP-specific CTL clone (BT7.4.1). The transgene-expressing CTL, specific for TNP/Kb were found to select for TcR alpha chains highly similar to that of the transgene donor clone BT7.4.1. In that way, two clones (II/7 and III/1) were identified whose TcR differed from the BT7.4.1 receptor only in their N alpha- and J alpha-sequences, i.e. within the third complementarity-determining regions of their alpha chains (CDR3 alpha). Moreover, the TcR of clones II/7 and III/1 had both rearranged the same J alpha element, thus differing from each other by only two amino acids in their V alpha/J alpha junctional regions. Functionally, however, clone III/1 exhibited unique cytolytic specificities for synthetic, Kb-binding TNP-peptides as well as for chemically TNP-modified allogeneic (H-2k) target cells. These findings demonstrate that (a) similar to "conventional" peptide antigens, synthetic hapten-peptide determinants are contacted by CDR3 alpha-determined amino acids of the TcR and (b) in contrast to current models, CDR alpha also appears to influence the major histocompatibility complex restriction specificity of a given TcR.