Polyclonal uses of T‐cell receptor (TCR)α and β genes for cytotoxic T lymphocytes in human metastatic melanoma: possible involvement of TCRα in tumor‐cell recognition

Identification of genetic structure and diversity of T‐cell receptor (TCR)α and β 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 TCRα and β 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. Vα7.2‐Jα10‐Cα was found in 4 of 22 clones, 2 of which also used the same β‐chain. The other 20 clones showed different combinations of α and β 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 TCRα. Eight of 13 clones used a threonine at the 99th or a serine residue at the 100th position in CDR3 of TCRα. CTL clones with the same or different TCRα 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 TCRα accumulate in the tumor.