ANTIGEN CONTACT SITES IN CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED, TRINITROPHENYL-SPECIFIC T-CELL RECEPTORS

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 K(b)-restricted, TNP-specific CTL clone (BT7.4.1). The transgene-expressing CTL, specific for TNP/K(b) 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 a 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, K(b)-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 haptenpeptide 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.