Zeng Gang, Li Yong, El-Gamil Mona, Sidney John, Sette Alexandro, Wang Rong-fu, Rosenberg Steven A, Robbins Paul F
Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Cancer Res. 2002 Jul 1;62(13):3630-5.
The existence of overlapping CD8+ and CD4+ T-cell epitopes within certain tumor antigens provides an opportunity to test the hypothesis that relatively short peptides could be used to generate both CD8+ and CD4+ T cells against tumor. In this report, T-cell responses to a fragment of the tumor antigen NY-ESO-1 that contained an HLA-DP4-restricted helper T cell epitope as well as an HLA-A2-restricted cytotoxic T cell epitope were analyzed. One peptide, ESO:157-170 (SLLMWITQCFLPVF) was recognized by both NY-ESO-1-reactive CD8+ and CD4+ T-cell clones. Both CD4+ and CD8+ T cells were efficiently generated from the peripheral blood of multiple melanoma patients after in vitro stimulations using ESO:157-170. Dual-specific peptides containing both cytotoxic T-cell and helper T-cell epitopes may represent an attractive strategy of vaccine design aimed at generating tumor-reactive CD4+ and CD8+ T cells.
某些肿瘤抗原中存在重叠的CD8⁺和CD4⁺T细胞表位，这为验证一个假说提供了机会，即相对短的肽可用于产生针对肿瘤的CD8⁺和CD4⁺T细胞。在本报告中，分析了T细胞对肿瘤抗原NY-ESO-1的一个片段的反应，该片段包含一个HLA-DP4限制性辅助性T细胞表位以及一个HLA-A2限制性细胞毒性T细胞表位。一种肽ESO:157-170（SLLMWITQCFLPVF）可被NY-ESO-1反应性CD8⁺和CD4⁺T细胞克隆识别。在使用ESO:157-170进行体外刺激后，多个黑色素瘤患者外周血中均有效地产生了CD4⁺和CD8⁺T细胞。包含细胞毒性T细胞和辅助性T细胞表位的双特异性肽可能代表了一种有吸引力的疫苗设计策略，旨在产生肿瘤反应性CD4⁺和CD8⁺T细胞。
