Clonal dominance of human autologous cytotoxic T lymphocytes against gastric carcinoma: Molecular stability of the CDR3 structure of the TCRαβ gene

In our previous study, RT-PCR suggested that cytotoxic T lymphocyte (CTL) clones may specifically recognize human autologous gastric signet ring cell tumor (HST2) by using TCR products of V(α)7 and V(β)20 subfamilies. In this report, we first determined the TCR nucleotide sequence of one such CTL clone, TcHST2. To study the clonal dominance and the TCR structural stability of HST2-specific CTL from patient's peripheral blood lymphocytes (PBL), the PBL were newly stimulated with a mixed lymphocyte-autologous tumor cell (HST2) culture (MLTC) and cytotoxic T cell lines, such as HPBL3x, were obtained. RT-PCR and the nucleotide sequence data indicated that HPBL3x also showed TCR V(α)7 and V(β)20 transcripts, and that HPBL3x TCR was composed of the exact same CDR3 gene structures as those of the TcHST2 clone. T cells with the same TCR structures were also detected in patient's non-treated peripheral blood, although they were infrequent. These data indicated that functional cytotoxic T cells with these distinct CDR3 equivalent structures were the dominant effector cells against HST2 autologous tumor cells. Moreover, the highly dominant and reproducible clonal expansion of T cells bearing heterodimeric TCR with identical variable, N diversity and constant region structures suggest that the molecular nature of governing antigenic peptide to TcHST2 may be stable and perhaps immunologically dominant in the interaction between CTL and HST2 autologous tumor cells.