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.
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.
复制标题
T 细胞受体 (TCR)α 和 β 基因在人类转移性黑色素瘤细胞毒性 T 淋巴细胞中的多克隆用途：TCR α 可能参与肿瘤细胞识别。
DOI：
10.1002/ijc.2910580407
复制
发表时间：
1994
影响因子：
6.4
通讯作者：
Itoh,K
中科院分区：
文献类型：
--
作者：
Seito,D;Morita,T;Masuoka,K;Maeda,T;Saya,H;Itoh,K
细胞毒性T淋巴细胞（CTL）浸润人类癌症的T细胞受体（TCR）α和β基因的遗传结构和多样性的鉴定对于更好地理解肿瘤部位宿主防御的分子机制非常重要。对从2名患者的肿瘤浸润淋巴细胞中建立的22个不同黑素瘤特异性CTL克隆的TCRα和β基因的cDNA进行测序，以分析其遗传结构和多样性。在22个克隆中的4个中发现Vα7.2-Jα10-Cα，其中2个也使用相同的β链。其他20个克隆表现出不同的α和β使用组合。在推导的氨基酸水平上，1例患者的9个克隆中有7个在TCRα互补决定区（CDR）1的第26位使用了苏氨酸残基。13个克隆中有8个克隆在TCRα的CDR 3的第99位使用苏氨酸或在第100位使用丝氨酸残基。具有相同或不同TCRα的CTL克隆分别表现出相同或不同的细胞毒活性。这些结果表明，在转移性黑色素瘤的肿瘤部位，CTL通常不表现出克隆性扩增，而是能够通过TCRα的CDR 3结合多种黑色素瘤决定簇的多克隆T细胞在肿瘤中积聚。
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.