CD8+ TCR Bias and Immunodominance in HIV-1 Infection.
CD8+ TCR Bias and Immunodominance in HIV-1 Infection.
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DOI：
10.4049/jimmunol.1400854
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发表时间：
2015-06-01
期刊：
影响因子：
--
通讯作者：
Goulder PJ
中科院分区：
文献类型：
--
作者：
Kløverpris HN;McGregor R;McLaren JE;Ladell K;Harndahl M;Stryhn A;Carlson JM;Koofhethile C;Gerritsen B;Keşmir C;Chen F;Riddell L;Luzzi G;Leslie A;Walker BD;Ndung'u T;Buus S;Price DA;Goulder PJ
免疫优势描述了一种现象，其中免疫系统始终仅靶向源自给定病原体的可用抗原库的一部分。在CD 8 + T细胞的情况下，这些受约束的表位靶向模式与人类白细胞抗原（HLA）I类表达相关，并决定疾病进展。尽管这些预定的反应层次的生物学重要性，但是，鲜为人知的是，在体内控制免疫优势的因素。在这项研究中，我们进行了广泛的分析，CD 8 + T细胞反应限制了一个单一的HLA I类分子，以评估机制，有助于表位靶向频率和抗病毒疗效的HIV-1感染。在HLA-B*42：01限制的20个不同表位中观察到明确的免疫优势等级，HLA-B*42：01在非洲起源的人群中非常普遍。此外，与先前的研究一致，GAG特异性应答和靶向宽度与较低的病毒载量设定点相关。然而，肽-HLA-B*42：01结合亲和力和稳定性与靶向频率没有显著联系。相反，免疫优势与公共TCR的表位特异性使用相关，公共TCR定义为在多个个体中出现的氨基酸残基相同的TRB序列。总的来说，这些结果提供了对重大人类感染中共享TCR募集、免疫优势和抗病毒功效之间潜在联系的第一次见解。
Immunodominance describes a phenomenon whereby the immune system consistently targets only a fraction of the available antigen pool derived from a given pathogen. In the case of CD8+ T-cells, these constrained epitope targeting patterns are linked to human leukocyte antigen (HLA) class-I expression and determine disease progression. Despite the biological importance of these predetermined response hierarchies, however, little is known about the factors that control immunodominance in vivo. In this study, we conducted an extensive analysis of CD8+ T-cell responses restricted by a single HLA class-I molecule to evaluate the mechanisms that contribute to epitope targeting frequency and antiviral efficacy in HIV-1 infection. A clear immunodominance hierarchy was observed across 20 different epitopes restricted by HLA-B*42:01, which is highly prevalent in populations of African origin. Moreover, in line with previous studies, Gag-specific responses and targeting breadth were associated with lower viral load set-points. However, peptide-HLA-B*42:01 binding affinity and stability were not significantly linked with targeting frequencies. Instead, immunodominance correlated with epitope-specific usage of public TCRs, defined as amino acid residue-identical TRB sequences that occur in multiple individuals. Collectively, these results provide the first insights into a potential link between shared TCR recruitment, immunodominance and antiviral efficacy in a major human infection.
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