Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, Japan; AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, Japan.
Microbes Infect. 2013 Nov;15(13):874-86. doi: 10.1016/j.micinf.2013.08.002. Epub 2013 Aug 19.
Identification of cross-clade T cell epitopes is one of key factors for the development of a widely applicable AIDS vaccine. We here investigated cross-clade CD8(+) T cell responses between clade B and A/E viruses in chronically HIV-1 clade A/E-infected Japanese individuals. CD8(+) T cell responses to 11-mer overlapping peptides derived from Nef, Gag, and Pol clade B consensus sequences were at a similar level to those to the same peptides found in clade B-infected individuals. Fifteen cross-clade CTL epitopes were identified from 13 regions where the frequency of responders was high in the clade A/E-infected individuals. The sequences of 6 epitopes were conserved between the clade B and clade A/E viruses whereas 9 epitopes had different amino acid sequences between the 2 viruses. CD8(+) T cells specific for the 6 conserved epitopes recognized cells infected with the clade A/E virus, whereas those for 8 diverse epitopes recognized both the clade A/E virus-infected and clade B-infected cells. All of the cross-clade CD8(+) T cells specific for conserved and diverse epitopes were detected in chronically HIV-1 clade A/E-infected individuals. These results show that in addition to conserved regions polymorphic ones across the clades can be targets for cross-clade CTLs.
鉴定跨谱系 T 细胞表位是开发广泛适用的艾滋病疫苗的关键因素之一。我们在此研究了慢性 HIV-1 谱系 A/E 感染者中谱系 B 和 A/E 病毒之间的跨谱系 CD8(+) T 细胞反应。来自 Nef、Gag 和 Pol 谱系 B 共识序列的 11 -mer 重叠肽的 CD8(+) T 细胞反应与在谱系 B 感染个体中发现的相同肽的反应水平相似。从谱系 A/E 感染个体中高应答者频率的 13 个区域中鉴定出 15 个跨谱系 CTL 表位。6 个表位的序列在谱系 B 和谱系 A/E 病毒之间保守,而 9 个表位在 2 种病毒之间具有不同的氨基酸序列。针对 6 个保守表位的 CD8(+) T 细胞识别感染了谱系 A/E 病毒的细胞,而针对 8 个不同表位的 CD8(+) T 细胞识别感染了谱系 A/E 病毒和谱系 B 病毒的细胞。在慢性 HIV-1 谱系 A/E 感染个体中检测到针对保守和多样化表位的所有跨谱系 CD8(+) T 细胞。这些结果表明,除了保守区域外,多态性区域也可以成为跨谱系 CTL 的靶标。