Kobayashi Hiroya, Nagato Toshihiro, Yanai Mitsuru, Oikawa Kensuke, Sato Keisuke, Kimura Shoji, Tateno Masatoshi, Omiya Ryusuke, Celis Esteban
Department of Pathology, Asahikawa Medical College, Asahikawa, Japan.
Clin Cancer Res. 2004 Oct 15;10(20):7053-62. doi: 10.1158/1078-0432.CCR-04-0897.
Human T-cell leukemia virus type I (HTLV-I) can cause an adult T-cell leukemia/lymphoma (ATLL). Because ATLL is a life-threatening lymphoproliferative disorder and is resistant to chemotherapy, the establishment and enhancement of T-cell immunity to HTLV-I through the development of therapeutic vaccines could be of value. Thus, the identification of HTLV-I epitopes for both CD8(+) and CD4(+) T cells should facilitate the development of effective vaccines. Although numerous HTLV-I epitopes for CTLs have been identified, few epitopes recognized by CD4(+) helper T cells against this virus have been described.
Synthetic peptides prepared from several regions of the HTLV-I envelope (Env) sequence that were predicted to serve as helper T-cell epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro helper T-cell responses using lymphocytes from normal volunteers.
The results show that the HTLV-I-Env(317-331), and HTLV-I-Env(384-398)-reactive helper T lymphocytes restricted by HLA-DQw6 and HLA-DR15, respectively, could recognize intact HTLV-I+ T-cell lymphoma cells and, as a consequence, secrete lymphokines. In addition, HTLV-I Env(196-210)-reactive helper T lymphocytes restricted by HLA-DR9 were able to directly kill HTLV-I+ lymphoma cells and recognize naturally processed antigen derived from killed HTLV-I+ lymphoma cells, which was presented to the helper T cells by autologous antigen-presenting cells.
The present findings hold relevance for the design and optimization of T-cell epitope-based immunotherapy against HTLV-I-induced diseases such as ATLL.
人类嗜T淋巴细胞病毒I型（HTLV-I）可引发成人T细胞白血病/淋巴瘤（ATLL）。由于ATLL是一种危及生命的淋巴细胞增殖性疾病且对化疗耐药，通过开发治疗性疫苗来建立和增强针对HTLV-I的T细胞免疫可能具有重要价值。因此，鉴定CD8(+)和CD4(+) T细胞的HTLV-I表位应有助于开发有效的疫苗。尽管已鉴定出许多针对细胞毒性T淋巴细胞（CTL）的HTLV-I表位，但针对该病毒的CD4(+)辅助性T细胞识别的表位却鲜有报道。
利用基于计算机的算法制备了从HTLV-I包膜（Env）序列的几个区域预测为辅助性T细胞表位的合成肽，并使用正常志愿者的淋巴细胞测试其触发体外辅助性T细胞反应的能力。
结果显示，分别受HLA-DQw6和HLA-DR15限制的对HTLV-I-Env(317-331)和HTLV-I-Env(384-398)产生反应的辅助性T淋巴细胞能够识别完整的HTLV-I+ T细胞淋巴瘤细胞，并因此分泌淋巴因子。此外，受HLA-DR9限制的对HTLV-I Env(196-210)产生反应的辅助性T淋巴细胞能够直接杀伤HTLV-I+淋巴瘤细胞，并识别来自被杀死的HTLV-I+淋巴瘤细胞的天然加工抗原，该抗原由自体抗原呈递细胞呈递给辅助性T细胞。
本研究结果与针对HTLV-I诱导的疾病如ATLL的基于T细胞表位的免疫疗法的设计和优化相关。
