CLONAL DOMINANCE OF HUMAN AUTOLOGOUS CYTOTOXIC T-LYMPHOCYTES AGAINST GASTRIC-CARCINOMA - MOLECULAR-STABILITY OF THE CDR3 STRUCTURE OF THE TCR-ALPHA-BETA GENE

In our previous study, RT-PCR suggested that cytotoxic T lymphocyte (C TL) clones may specifically recognize human autologous gastric signet ring cell tumor (HST2) by using TCR products of V(alpha)7 and V(beta)2 0 subfamilies, In this report, we first determined the TCR nucleotide sequence of one such CTL clone, TcHST2. To study the clonal dominance and the Ton structural stability of HST2-specific CTL from patient's p eripheral blood lymphocytes (PBL), the PBL were newly stimulated with a mixed lymphocyte-autologous tumor cell (HSTP) culture (MLTC) and cyt otoxic T cell lines, such as HPBL3x, were obtained, RT-PCR and the nuc leotide sequence data indicated that HPBL3x also showed TCR V(alpha)7 and V(beta)20 transcripts, and that HPBL3x TCR was composed of the exa ct same CDR3 gene structures as those of the TcHST2 clone, T cells wit h 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 HSTP autologous tu mor cells, Moreover, the highly dominant and reproducible clonal expan sion of T cells bearing heterodimeric TCR with identical variable, N d iversity and constant region structures suggest that the molecular nat ure of governing antigenic peptide to TcHST2 may be stable and perhaps immunologically dominant in the interaction between CTL and HSTP auto logous tumor cells.