Broad and Gag-biased HIV-1 epitope repertoires are associated with lower viral loads.
Broad and Gag-biased HIV-1 epitope repertoires are associated with lower viral loads.
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DOI：
10.1371/journal.pone.0001424
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发表时间：
2008-01-09
期刊：
影响因子：
3.7
通讯作者：
Mullins, James I.
中科院分区：
文献类型：
--
作者：
Rolland, Morgane;Heckerman, David;Deng, Wenjie;Rousseau, Christine M.;Coovadia, Hoosen;Bishop, Karen;Goulder, Philip J. R.;Walker, Bruce D.;Brander, Christian;Mullins, James I.
HLA - i类等位基因通过细胞介导的免疫反应控制HIV复制的能力不同。细胞毒性T淋巴细胞（CTL）反应的广度与HIV-1的控制之间没有一致的关联，而且尚不清楚病毒蛋白组范围表位库的大小或分布，即呈现更少、更多或特异性病毒表位的内在能力，是否会影响疾病进展的临床标志物。根据每个人的HLA（人类白细胞抗原）基因型，我们使用表位预测模型鉴定了一组302个HIV-1全长蛋白质组中的所有表位基序。表位库，即每个HIV-1蛋白质组预测表位的数量，在HLA等位基因之间以及在单个蛋白质组之间存在很大差异。在一个由270名慢性感染者组成的亚组中，我们发现较低的病毒载量和较高的CD4计数与较大的预测表位库相关。此外，仅在Gag和Rev中，受低病毒载量相关等位基因限制的表位比受高病毒载量相关等位基因限制的表位多。这一综合分析提出表位库作为多方面的hiv特异性CTL反应的机制组成部分。倾向于呈现更多HLA结合肽和特异性蛋白对疾病状态标记物的有利影响，推动了寻求引起对广泛的HIV-1表位的反应的疫苗设计策略，并建议特别关注Gag。
HLA class-I alleles differ in their ability to control HIV replication through cell-mediated immune responses. No consistent associations have been found between the breadth of Cytotoxic T Lymphocytes (CTL) responses and the control of HIV-1, and it is unknown whether the size or distribution of the viral proteome-wide epitope repertoire, i.e., the intrinsic ability to present fewer, more or specific viral epitopes, could affect clinical markers of disease progression. We used an epitope prediction model to identify all epitope motifs in a set of 302 HIV-1 full-length proteomes according to each individual's HLA (Human Leukocyte Antigen) genotype. The epitope repertoire, i.e., the number of predicted epitopes per HIV-1 proteome, varied considerably between HLA alleles and thus among individual proteomes. In a subgroup of 270 chronically infected individuals, we found that lower viral loads and higher CD4 counts were associated with a larger predicted epitope repertoire. Additionally, in Gag and Rev only, more epitopes were restricted by alleles associated with low viral loads than by alleles associated with higher viral loads. This comprehensive analysis puts forth the epitope repertoire as a mechanistic component of the multi-faceted HIV-specific CTL response. The favorable impact on markers of disease status of the propensity to present more HLA binding peptides and specific proteins gives impetus to vaccine design strategies that seek to elicit responses to a broad array of HIV-1 epitopes, and suggest a particular focus on Gag.
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