Affinity, specificity and T-cell-receptor diversity of melanoma-specific CTL generated in vitro against a single tyrosinase epitope.

Autor: Visseren MJ; Department of Immunohematology and Blood Bank, Leiden University Hospital, The Netherlands., van der Burg SH, Hawes GE, van der Voort EI, van den Elsen PJ, Melief CJ
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 1997 Sep 17; Vol. 72 (6), pp. 1122-8.
DOI: 10.1002/(sici)1097-0215(19970917)72:6<1122::aid-ijc30>3.0.co;2-3
Abstrakt: MHC-class-I-restricted cytotoxic T lymphocytes (CTL) specific for tumor-associated antigens expressed by malignant cells are important components 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 peptide-specific stimulation in vitro can induce high-affinity CTL capable of recognizing tumor cells expressing the appropriate tumor antigen. These tyrosinase-specific CTL display a restricted usage of TCRAV and TCRBV gene segments but of diverse CDR3 regions, resulting in a distinct 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 autologous tumors. The generated CTL can recognize their target structure with high affinity, and this correlates in part with tumor-cell lysis. This methodology may be used to treat melanoma patients with infusion of ex vivo-induced and -expanded CTL.
Databáze: MEDLINE