A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape.
A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape.
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DOI：
10.1186/s12977-015-0149-5
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发表时间：
2015-02-20
期刊：
影响因子：
3.3
通讯作者：
Goulder P
中科院分区：
文献类型：
--
作者：
Kløverpris HN;Cole DK;Fuller A;Carlson J;Beck K;Schauenburg AJ;Rizkallah PJ;Buus S;Sewell AK;Goulder P
通过密切相关的人类白细胞抗原I类（HLAI）分子呈递相同的HIV-1肽可以选择不同的逃逸突变模式，这对病毒适应性和疾病进展有重大影响。HLAI微多态性在相同肽表位内诱导不同HIV-1逃逸模式的分子机制尚不清楚。在这里，我们对两个免疫优势的HIV-1肽进行了遗传和结构分析，Gag180-188 （TPQDLNTML, TL9-p24）和Nef71-79 （RPQVPLRPM, RM9-Nef）是全球HIV-1流行中最高度靶向的表位之一。我们发现HLA-B7超家族的不同等位基因之间的单多态性可以诱导肽构象的转换，这与不同的hla特异性逃逸突变和免疫控制有关。在HLA-B*07:02的人群中，Nef71-79存在显性R71K突变，而在B*42:01/02和B*81:01的人群中不存在。没有检测到hla表位复合物的结构差异来解释这一观察结果。这些数据表明，通过非常相似的HLAI景观呈现的相同肽被认为是不同的表位，并为先前观察到的差异HIV-1逃逸和疾病进展提供了新的结构机制。本文的在线版本（doi:10.1186/s12977-015-0149-5）包含补充材料，可供授权用户使用。
Presentation of identical HIV-1 peptides by closely related Human Leukocyte Antigen class I (HLAI) molecules can select distinct patterns of escape mutation that have a significant impact on viral fitness and disease progression. The molecular mechanisms by which HLAI micropolymorphisms can induce differential HIV-1 escape patterns within identical peptide epitopes remain unknown. Here, we undertook genetic and structural analyses of two immunodominant HIV-1 peptides, Gag180–188 (TPQDLNTML, TL9-p24) and Nef71–79 (RPQVPLRPM, RM9-Nef) that are among the most highly targeted epitopes in the global HIV-1 epidemic. We show that single polymorphisms between different alleles of the HLA-B7 superfamily can induce a conformational switch in peptide conformation that is associated with differential HLAI-specific escape mutation and immune control. A dominant R71K mutation in the Nef71-79 occurred in those with HLA-B*07:02 but not B*42:01/02 or B*81:01. No structural difference in the HLA-epitope complexes was detected to explain this observation. These data suggest that identical peptides presented through very similar HLAI landscapes are recognized as distinct epitopes and provide a novel structural mechanism for previously observed differential HIV-1 escape and disease progression. The online version of this article (doi:10.1186/s12977-015-0149-5) contains supplementary material, which is available to authorized users.
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影响因子：
2.2
作者：
Bulek, Anna M.;Madura, Florian;Fuller, Anna;Holland, J.;Schauenburg, Andrea J. A.;Sewell, Andrew K.;Rizkallah, Pierre J.;Cole, David K.
通讯作者：
Cole, David K.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
158.5
作者：
Gao, XJ;Nelson, GW;Carrington, M
通讯作者：
Carrington, M
影响因子：
4.4
作者：
Honeyborne, Isobella;Rathod, Almas;Goulder, Philip J. R.
通讯作者：
Goulder, Philip J. R.
影响因子：
1.5
作者：
Kloverpris, Henrik N.;Adland, Emily;Goulder, Philip
通讯作者：
Goulder, Philip