Robbins P F, el-Gamil M, Kawakami Y, Stevens E, Yannelli J R, Rosenberg S A
Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Res. 1994 Jun 15;54(12):3124-6.
The observation that allogeneic melanoma cells matched for particular HLA class I alleles stimulate T-cells isolated from patients suggests that widely shared antigens exist on these tumors. A transient expression system was developed for screening a melanoma complementary DNA library using the highly transfectable human kidney cell line 293. Using this system, large numbers of complementary DNA clones can be rapidly screened for the expression of antigens which stimulate T-cells. Tumor-infiltrating lymphocytes from patient 888, which recognized melanoma in the context of HLA-A24, were used to screen a complementary DNA library made from the autologous melanoma. Our results demonstrate that these tumor-infiltrating lymphocytes recognize tyrosinase, a gene previously shown to be recognized by T-cells only in the context of HLA-A2. These data demonstrate that a single antigen can be recognized in the context of two different class I HLA alleles. In addition, this study suggests that recognition of tyrosinase by antigen-specific T-cells may be involved in tumor rejection.
特定HLA I类等位基因匹配的同种异体黑色素瘤细胞能刺激从患者体内分离出的T细胞，这一观察结果表明这些肿瘤上存在广泛共享的抗原。利用高度可转染的人肾细胞系293开发了一种瞬时表达系统，用于筛选黑色素瘤互补DNA文库。使用该系统，可以快速筛选大量互补DNA克隆，以检测刺激T细胞的抗原的表达。来自患者888的肿瘤浸润淋巴细胞在HLA - A24背景下识别黑色素瘤，用其筛选来自自体黑色素瘤的互补DNA文库。我们的结果表明，这些肿瘤浸润淋巴细胞识别酪氨酸酶，该基因先前仅在HLA - A2背景下被T细胞识别。这些数据表明，单一抗原可以在两种不同的I类HLA等位基因背景下被识别。此外，本研究表明抗原特异性T细胞对酪氨酸酶的识别可能参与肿瘤排斥反应。
