Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes.
Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes.
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DOI：
10.1084/jem.179.3.1005
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发表时间：
1994-03-01
期刊：
影响因子：
--
通讯作者：
Figdor CG
中科院分区：
文献类型：
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作者：
Bakker AB;Schreurs MW;de Boer AJ;Kawakami Y;Rosenberg SA;Adema GJ;Figdor CG
我们最近分离了一个编码黑素细胞谱系特异性抗原糖蛋白（gp）100的cDNA克隆。针对gp100的抗体是诊断人类黑色素瘤的重要工具。由于gp100抗原在黑素细胞中高度表达，我们研究了该抗原是否可以作为抗黑素瘤细胞毒性T淋巴细胞（CTL）的靶标。在这里，我们证明来自黑色素瘤患者（TIL 1200）的细胞毒性肿瘤浸润淋巴细胞（TIL）直接针对gp100。HLA-A2.1+黑色素瘤细胞被TIL溶解。此外，同时表达HLA-A2.1和gp100的小鼠双转染可以被TIL 1200裂解，而仅表达HLA-A2.1的转染则不容易被裂解。此外，缺乏gp100表达且抗裂解的HLA-A2.1+黑色素瘤细胞系BLM在转染gp100 cDNA后变得易感。最后，TIL 1200溶解HLA-A2.1+正常黑素细胞。这些数据表明黑素细胞分化抗原gp100可以通过来自黑色素瘤患者的CTL在HLA-A2.1的背景下识别。因此，Gp100可能构成针对黑色素瘤的特异性免疫治疗的有用靶点，前提是没有观察到对正常组织的不可接受的细胞毒性。
We recently isolated a cDNA clone that encodes the melanocyte lineage- specific antigen glycoprotein (gp)100. Antibodies directed against gp100 are an important tool in the diagnosis of human melanoma. Since the gp100 antigen is highly expressed in melanocytic cells, we investigated whether this antigen might serve as a target for antimelanoma cytotoxic T lymphocytes (CTL). Here, we demonstrate that cytotoxic tumor-infiltrating lymphocytes (TIL) derived from a melanoma patient (TIL 1200) are directed against gp100. HLA-A2.1+ melanoma cells are lysed by TIL from this patient. In addition, murine double transfectants, expressing both HLA-A2.1 and gp100, are lysed by TIL 1200, whereas transfectants expressing only HLA-A2.1 are not susceptible to lysis. Furthermore, the HLA-A2.1+ melanoma cell line BLM, which lacks gp100 expression and is resistant to lysis, becomes susceptible after transfection of gp100 cDNA. Finally, HLA-A2.1+ normal melanocytes are lysed by TIL 1200. These data demonstrate that the melanocyte differentiation antigen gp100 can be recognized in the context of HLA-A2.1 by CTL from a melanoma patient. Gp100 may therefore constitute a useful target for specific immunotherapy against melanoma, provided that no unacceptable cytotoxicity towards normal tissue is observed.