T-cell receptor gene structures of HLA-A26-restricted cytotoxic T lymphocyte lines against human autologous pancreatic adenocarcinoma.

We isolated two cytotoxic T lymphocyte (CTL) lines, which were independently obtained by mixed lymphocyte-tumor cell culture from tumor-infiltrating lymphocytes of a patient with pancreatic adenocarcinoma. Both lines behaved identically in all the functional aspects tested and appeared to be HLA-A26-restricted. We analyzed their T cell receptor (TCR) gene structures, including V-(D)-J junctional sequences, which are unique to each T-cell clonotype and contribute to TCR diversity. Each line consisted of a clonal T-cell expressing V alpha 18 and V beta 7. The alpha chain gene was composed of V alpha 18/J alpha F/C alpha and the beta-chain gene, of V beta 7.1/D beta/J beta 1.4/C beta 2. The sequences were all in-frame and therefore should yield functional transcripts. The junctional sequences were identical between the two lines. These data suggested that the two CTL clones having the same CDR3 had descended from a common precursor lymphocyte. The clonal expansion of CTL lines with the identical CDR3 implies that they are directed against the same tumor antigen, which seemed to be immunologically dominant in the specific interaction between the CTL and the autologous pancreatic adenocarcinoma.