Darrow T L, Slingluff C L, Seigler H F
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
J Immunol. 1989 May 1;142(9):3329-35.
CTL lines were established in vitro by stimulating patient lymphocytes with autologous melanoma cells in the presence of IL-2. Resulting CTL lines lysed autologous melanoma and failed to lyse several allogeneic melanomas or K562. The mechanism of target cell recognition by autologous tumor-specific CTL was evaluated in this system, using several CTL lines: DT6, DT105, DT141, DT166, DT169, and DT179. Autologous melanoma lysis was inhibited by W6/32, mAb directed against HLA class I Ag, but not by L243, mAb directed against HLA class II Ag. CTL from DT6, DT141, DT166, DT169, and DT179 lysed fresh and cultured allogeneic melanomas, which shared the HLA-A2 Ag, but failed to lyse allogeneic melanomas, which shared B-region or C-region Ag, or shared no HLA class I Ag. CTL from DM141 lysed DM93, which shared A2 and Bw6, but failed to lyse DM105, which shared only Bw6. DM105 CTL failed to lyse allogeneic melanomas that shared HLA-A1, or that shared B or C region Ag, but they did lyse allogeneic melanoma DM49, which expressed an A region Ag that either was A10 or was serologically cross-reactive with A10. A T cell leukemia line, three EBV transformed B cell lines, and a pancreatic cancer line, all of which expressed HLA-A2, were not lysed by DM6 or DM179 CTL. Furthermore, HLA-matched nonmelanomas failed to inhibit autologous tumor lysis in cold target inhibition assays, whereas an HLA-A2+ allogeneic melanoma, DM93, inhibited autologous tumor lysis as effectively as the autologous tumor itself. HLA-A2, and possibly other HLA-A-region Ag, appear to function in HLA-restricted recognition of shared melanoma associated Ag by CTL.
通过在白细胞介素-2存在的情况下，用自体黑色素瘤细胞刺激患者淋巴细胞，在体外建立细胞毒性T淋巴细胞（CTL）系。所得的CTL系可裂解自体黑色素瘤，但不能裂解几种同种异体黑色素瘤或K562细胞。使用多个CTL系（DT6、DT105、DT141、DT166、DT169和DT179）在该系统中评估自体肿瘤特异性CTL识别靶细胞的机制。针对HLA I类抗原的单克隆抗体W6/32可抑制自体黑色素瘤的裂解，但针对HLA II类抗原的单克隆抗体L243则不能。来自DT6、DT141、DT166、DT169和DT179的CTL可裂解新鲜的和培养的、共享HLA-A2抗原的同种异体黑色素瘤，但不能裂解共享B区或C区抗原或不共享任何HLA I类抗原的同种异体黑色素瘤。来自DM141的CTL可裂解共享A2和Bw6的DM93，但不能裂解仅共享Bw6的DM105。DM105 CTL不能裂解共享HLA-A1或共享B或C区抗原的同种异体黑色素瘤，但它们可裂解表达A区抗原（该抗原要么是A10，要么与A10血清学交叉反应）的同种异体黑色素瘤DM49。一个T细胞白血病系、三个EB病毒转化的B细胞系和一个胰腺癌细胞系，所有这些细胞系均表达HLA-A2，但未被DM6或DM179 CTL裂解。此外，在冷靶抑制试验中，HLA匹配的非黑色素瘤细胞不能抑制自体肿瘤的裂解，而一个HLA-A2+同种异体黑色素瘤DM93抑制自体肿瘤裂解的效果与自体肿瘤本身一样有效。HLA-A2以及可能的其他HLA-A区抗原似乎在CTL对共享的黑色素瘤相关抗原的HLA限制性识别中发挥作用。
