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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

✍ Scribed by Dai Seito; Tatsuo Morita; Kazuhiro Masuoka; Tomoyuki Maeda; Hideyuki Saya; Kyogo Itoh


Publisher
John Wiley and Sons
Year
1994
Tongue
French
Weight
675 KB
Volume
58
Category
Article
ISSN
0020-7136

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✦ Synopsis


Identification of genetic structure and diversity of T-cell receptor (TCR)a and p 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 TCRu and p genes of 22 different melanoma-specific CTL clones established from the tumorinfiltrating lymphocytes of 2 patients were sequenced for analysis of their genetic structure and diversity. Va7.2-Ja 10-C CY was found in 4 of 22 clones, 2 of which also used the same f3-chain. The other 20 clones showed different combinations of a and p 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) I of TCRa. Eight of I3 clones used a threonine at the 99th or a serine residue at the 100th position in CDR3 of TCRa CTL clones with the same or different TCRn 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 TCRa accumulate in the tumor. < 1904 It'rk?.-l.rts. Ill(


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Tumor-infiltrating lymphocytes (TlL) freshly obtained from human malignant melanomas as well as the same TIL grown in the presence of interleukin 2 (IL2) were studied for gene expression of the T-cell receptor (TCR) variable P regions (VP). To perform the TCR-VP analysis, total RNA was isolated fro