Takahashi T, Chapman P B, Yang S Y, Hara I, Vijayasaradhi S, Houghton A N
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
J Immunol. 1995 Jan 15;154(2):772-9.
Reactivity of CD8+ T lymphocytes against human melanoma has been extensively characterized, but little is known about melanoma Ags recognized by CD4+ lymphocytes. We have identified CD4+ CTL that recognize shared melanoma Ag(s) expressed by autologous melanoma cells and a subset of allogeneic melanomas. The same Ag(s) was shared by autologous and positive allogeneic melanomas by cross-blocking experiments. Cytotoxicity was directed against epitopes presented by HLA-DR on target melanoma cells, and allelic typing revealed that cytotoxicity was restricted through HLA-DR15. These CD4+ T cells released IFN-gamma, IL-4, and TNF-alpha, but not IL-2, in response to HLA-DR15+ target cells. CD4+ T cells did not lyse DR15+ nonmelanoma cell types, including melanocytes or fibroblasts (induced to express HLA-DR by IFN-gamma). Thus, by cytotoxicity assays, shared Ags were only recognized on melanoma cells but not on normal melanocytes. In summary, this analysis shows that melanoma cells share an Ag that is presented by HLA-DR15.
CD8 + T淋巴细胞对人黑色素瘤的反应性已得到广泛研究，但对于CD4 +淋巴细胞识别的黑色素瘤抗原却知之甚少。我们已经鉴定出能够识别由自体黑色素瘤细胞和一部分同种异体黑色素瘤共同表达的黑色素瘤抗原的CD4 +细胞毒性T淋巴细胞（CTL）。通过交叉阻断实验发现，自体和阳性同种异体黑色素瘤共享相同的抗原。细胞毒性作用针对靶黑色素瘤细胞上由HLA - DR呈递的表位，等位基因分型显示细胞毒性作用受HLA - DR15限制。这些CD4 + T细胞在接触HLA - DR15 +靶细胞时释放γ干扰素、白细胞介素 - 4和肿瘤坏死因子 - α，但不释放白细胞介素 - 2。CD4 + T细胞不会裂解DR15 +非黑色素瘤细胞类型，包括黑素细胞或成纤维细胞（通过γ干扰素诱导表达HLA - DR）。因此，通过细胞毒性分析，共享抗原仅在黑色素瘤细胞上被识别，而在正常黑素细胞上未被识别。总之，该分析表明黑色素瘤细胞共享一种由HLA - DR15呈递的抗原。
