Paludan Casper, Bickham Kara, Nikiforow Sarah, Tsang Ming L, Goodman Kiera, Hanekom Willem A, Fonteneau Jean-Francois, Stevanović Stefan, Münz Christian
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
J Immunol. 2002 Aug 1;169(3):1593-603. doi: 10.4049/jimmunol.169.3.1593.
The gamma-herpesvirus, EBV, is reliably found in a latent state in endemic Burkitt's lymphoma. A single EBV gene product, Epstein-Barr nuclear Ag 1 (EBNA1), is expressed at the protein level. Several mechanisms prevent immune recognition of these tumor cells, including a block in EBNA1 presentation to CD8(+) killer T cells. Therefore, no EBV-specific immune response has yet been found to target Burkitt's lymphoma. We now find that EBNA1-specific, Th1 CD4(+) cytotoxic T cells recognize Burkitt's lymphoma lines. CD4(+) T cell epitopes of EBNA1 are predominantly found in the C-terminal, episome-binding domain of EBNA1, and approximately 0.5% of peripheral blood CD4(+) T cells are specific for EBNA1. Therefore, adaptive immunity can be directed against Burkitt's lymphoma, and perhaps this role for CD4(+) Th1 cells extends to other tumors that escape MHC class I presentation.
γ-疱疹病毒EBV在地方性伯基特淋巴瘤中可靠地以潜伏状态存在。单个EBV基因产物，即EB病毒核抗原1（EBNA1），在蛋白质水平表达。多种机制可防止这些肿瘤细胞被免疫识别，包括阻止EBNA1呈递给CD8(+)杀伤性T细胞。因此，尚未发现针对伯基特淋巴瘤的EBV特异性免疫反应。我们现在发现，EBNA1特异性的Th1 CD4(+)细胞毒性T细胞可识别伯基特淋巴瘤细胞系。EBNA1的CD4(+) T细胞表位主要位于EBNA1的C末端附加体结合结构域，约0.5%的外周血CD4(+) T细胞对EBNA1具有特异性。因此，适应性免疫可以针对伯基特淋巴瘤，也许CD4(+) Th1细胞的这种作用可扩展到其他逃避MHC I类呈递的肿瘤。
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