Wang R F, Robbins P F, Kawakami Y, Kang X Q, Rosenberg S A
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1995 Feb 1;181(2):799-804. doi: 10.1084/jem.181.2.799.
The availability of antitumor cytotoxic T lymphocytes which can be generated from either peripheral blood lymphocytes after stimulation in vitro or tumor infiltrating lymphocytes (TIL) has made it possible to identify a number of melanoma antigens presented by major histocompatibility complex class I molecules. The present and previous studies indicated that TIL586 recognized an antigen expressed on most melanoma and normal melanocytes in the context of the HLA-A31 molecule. We report here the cloning of a cDNA that directs the expression of the shared melanoma antigen recognized by this TIL. The DNA sequence analysis revealed that the cDNA was almost identical to the gene encoding tyrosinase-related protein 1 or glycoprotein gp75 which was originally identified by serum antibodies in a patient with melanoma. The gene was found to be expressed only in melanoma, normal melanocyte cell lines, and retina, but not in other normal tissues tested. The gp75 antigen presented by HLA-A31 may therefore constitute a useful immune target for specific treatment of patients with melanoma, since both antibody- and T cell-mediated immune responses can be generated against this antigen.
通过体外刺激外周血淋巴细胞或肿瘤浸润淋巴细胞（TIL）产生抗肿瘤细胞毒性T淋巴细胞，使得识别主要组织相容性复合体I类分子呈递的多种黑色素瘤抗原成为可能。目前及之前的研究表明，TIL586在HLA - A31分子的背景下识别大多数黑色素瘤和正常黑素细胞上表达的一种抗原。我们在此报告一种cDNA的克隆，该cDNA指导这种TIL识别的共享黑色素瘤抗原的表达。DNA序列分析显示，该cDNA与编码酪氨酸酶相关蛋白1或糖蛋白gp75的基因几乎相同，后者最初是在一名黑色素瘤患者中通过血清抗体鉴定出来的。发现该基因仅在黑色素瘤、正常黑素细胞系和视网膜中表达，而在其他测试的正常组织中不表达。因此，由HLA - A31呈递的gp75抗原可能构成黑色素瘤患者特异性治疗的有用免疫靶点，因为针对该抗原可产生抗体介导和T细胞介导的免疫反应。
