The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas.
The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas.
复制标题
DOI：
10.1084/jem.178.2.489
复制
发表时间：
1993-08-01
期刊：
影响因子：
--
通讯作者：
Boon T
中科院分区：
文献类型：
--
作者：
Brichard V;Van Pel A;Wölfel T;Wölfel C;De Plaen E;Lethé B;Coulie P;Boon T
黑色素瘤患者的淋巴细胞可以在体外用自体肿瘤细胞再刺激以产生抗肿瘤的溶细胞性T淋巴细胞（CTL）。先前的报道已经表明，当从HLA-A2黑素瘤患者获得这样的CTL时，它们通常在A2黑素瘤细胞系上显示出广泛的反应性。从两名患者中分离出似乎识别相同抗原的这种抗肿瘤CTL克隆。我们在这里报告的cDNA，指导这些CTL识别的抗原的表达的克隆。该cDNA对应于酪氨酸酶基因的转录物。发现该基因在所有测试的黑色素瘤样品和大多数黑色素瘤细胞系中是活跃的。在正常细胞中，只有黑素细胞似乎表达该基因。因此，酪氨酸酶抗原提出的HLA-A2可能构成一个有用的目标，特异性免疫治疗黑色素瘤。但是，抗酪氨酸酶免疫接种可能产生的不良反应，如正常黑素细胞的破坏及其后果，必须在进行临床试验研究之前进行检查。
Lymphocytes of melanoma patients can be restimulated in vitro with autologous tumor cells to generate antitumor cytolytic T lymphocytes (CTL). Previous reports have indicated that, when such CTL are obtained from HLA-A2 melanoma patients, they often display broad reactivity on A2 melanoma cell lines. Such antitumor CTL clones, which appeared to recognize the same antigen, were isolated from two patients. We report here the cloning of a cDNA that directs the expression of the antigen recognized by these CTL. This cDNA corresponds to the transcript of the tyrosinase gene. The gene was found to be active in all tested melanoma samples and in most melanoma cell lines. Among normal cells, only melanocytes appear to express the gene. The tyrosinase antigen presented by HLA-A2 may therefore constitute a useful target for specific immunotherapy of melanoma. But possible adverse effects of antityrosinase immunization, such as the destruction of normal melanocytes and its consequences, will have to be examined before clinical pilot studies can be undertaken.