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T cell receptor usage by cytotoxic T lymphocytes against autologous human melanoma
S P Leong1, J Liliental, S M Krams
1Department of Surgery, University of California, San Francisco/Mount Zion Cancer Center 94120, USA.
Background:
T cell receptor (TCR) usage by tumor infiltrating lymphocytes (TIL) represents the host's response to autologous melanoma (AM). The goal of this study is it determine TCR usage by cytotoxic T lymphocytes (CTL) against AM.
Materials And Methods:
CTL were generated from three patients using lymphocytes from metastatic or tumor-draining lymph nodes by repeated in vitro sensitization (IVS). Total RNA was isolated from CTL and reverse-transcribed to cDNA. TCR usage was determined by polymerase chain reaction (PCR) using TCR primers.
Results:
Cytolytic activity was non-specific within the first 2-4 weeks following IVS and TCR repertoire in these cultures revealed random V alpha and V beta gene usage. In contrast, by 6-10 weeks of culture, cytolysis was specifically directed against AM cells and such specific cytolysis was significantly correlated with TCR V alpha 1 (P < 0.001).
Conclusion:
TCR V alpha 1 is associated with a common restricted melanoma antigen.