AFFINITY SPECIFICITY AND T-CELL-RECEPTOR DIVERSITY OF MELANOMA-SPECIFIC CTL GENERATED IN-VITRO AGAINST A SINGLE TYROSINASE EPITOPE

MHC-class-l-restricted cytotoxic T lymphocytes (CTL) specific for tumo r-associated antigens expressed by malignant cells are important compo nents of the immune response against cancer, Recently, tumor-specific CTL could be generated in vitro, with responding lymphocytes from the blood of healthy blood donors, In the present study, we confirm that p eptide-specific stimulation in vitro can induce high-affinity CTL capa ble of recognizing tumor cells expressing the appropriate tumor antige n, These tyrosinase-specific CTL display a restricted usage of TCRAV a nd TCRBV gene segments but of diverse CDR3 regions, resulting in a dis tinct fine-specificity for each CTL clone, This suggests that, similar to in vivo priming, peptide-pulsed APC are capable of stimulating a T -cell response in vitro expressing a limited TCR repertoire against au tologous tumors, The generated CTL can recognize their target structur e with high affinity, and this correlates in part with tumor-cell lysi s, This methodology may be used to treat melanoma patients with infusi on of ex vivo-induced and -expanded CTL. (C) 1997 Wiley-Liss, Inc.