与艾滋病进展延迟相关的人类白细胞抗原（HLA）等位基因对初始抗HIV-1的CD8(+) T细胞反应有很大贡献。

HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1.

作者信息

Altfeld Marcus, Kalife Elizabeth T, Qi Ying, Streeck Hendrik, Lichterfeld Mathias, Johnston Mary N, Burgett Nicole, Swartz Martha E, Yang Amy, Alter Galit, Yu Xu G, Meier Angela, Rockstroh Juergen K, Allen Todd M, Jessen Heiko, Rosenberg Eric S, Carrington Mary, Walker Bruce D

出版信息

PLoS Med. 2006 Oct;3(10):e403. doi: 10.1371/journal.pmed.0030403.

BACKGROUND

Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression.

METHODS AND FINDINGS

In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8(+) T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8(+) T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8(+) T cell response during primary infection.

CONCLUSIONS

These data demonstrate consistent immunodominance patterns of HIV-1-specific CD8(+) T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression.

背景

关于原发性HIV-1感染期间HIV-1特异性T细胞反应的免疫显性模式以及人类淋巴细胞抗原（HLA）调节疾病进展的原因，人们了解甚少。

方法与发现

在一个由104名原发性HIV-1感染个体组成的队列中，我们证明HIV-1内的一部分CD8(+) T细胞表位在感染后早期始终是靶向目标，而通过相同的HLA I类等位基因随后靶向的其他表位则很少被识别。在原发性感染期间，某些HLA等位基因对总的病毒特异性CD8(+) T细胞反应的贡献始终大于其他等位基因，并且如果在同一个体中共表达，还会降低受其他等位基因限制的反应的绝对强度，这与免疫显性一致。此外，与HIV-1疾病进展较慢相关的个体HLA I类等位基因在原发性感染期间对总的HIV-1特异性CD8(+) T细胞反应有很大贡献。