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 indepen dently obtained by mixed lymphocyte-tumor cell culture from tumor-infi ltrating lymphocytes of a patient with pancreatic adenocarcinoma. Both lines behaved identically in all the functional aspects tested and ap peared to be HLA-A26-restricted. We analyzed their T cell receptor (TC R) 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 seq uences were all in-frame and therefore should yield functional transcr ipts. The junctional sequences were identical between the two lines. T hese data suggested that the two CTL clones having the same CDR3 had d escended from a common precursor lymphocyte. The clonal expansion of C TL lines with the identical CDR3 implies that they are directed agains t the same tumor antigen, which seemed to be immunologically dominant in the specific interaction between the CTL and the autologous pancrea tic adenocarcinoma.