Polyclonal uses of T-cell receptor (TCR)alpha and beta genes for cytotoxic T lymphocytes in human metastatic melanoma: possible involvement of TCR alpha in tumor-cell recognition.

Identification of genetic structure and diversity of T-cell receptor (TCR)alpha and beta genes for cytotoxic T lymphocytes (CTLs) infiltrating human cancers is important for the better understanding of molecular mechanisms of host defense at tumor sites. cDNAs of TCR alpha and beta genes of 22 different melanoma-specific CTL clones established from the tumor-infiltrating lymphocytes of 2 patients were sequenced for analysis of their genetic structure and diversity. V alpha 7.2-J alpha 10-C alpha was found in 4 of 22 clones, 2 of which also used the same beta-chain. The other 20 clones showed different combinations of alpha and beta use. At deduced amino-acid levels, 7 of 9 clones from one patient used a threonine residue at the 26th position in the complementarity-determining region (CDR)1 of TCR alpha. Eight of 13 clones used a threonine at the 99th or a serine residue at the 100th position in CDR3 of TCR alpha CTL clones with the same or different TCR alpha showed the same or different patterns of cytotoxicity, respectively. These results suggest that CTLs usually do not demonstrate clonal expansion at tumor sites of metastatic melanoma's but rather that polyclonal T cells capable of binding to multiple melanoma determinants through CDR3 of TCR alpha accumulate in the tumor.