An Early HIV Mutation within an HLA-B*57-Restricted T Cell Epitope Abrogates Binding to the Killer Inhibitory Receptor 3DL1
An Early HIV Mutation within an HLA-B*57-Restricted T Cell Epitope Abrogates Binding to the Killer Inhibitory Receptor 3DL1
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DOI：
10.1128/jvi.00238-11
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Gillespie, Geraldine M.
中科院分区：
文献类型：
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作者：
Brackenridge, Simon;Evans, Edward J.;Gillespie, Geraldine M.
已经研究了MHC i类限制性表位内的突变与T细胞介导的免疫逃逸的关系，但在早期HIV感染期间，它们通过与杀伤igg样受体（KIRs）相互作用对NK细胞的影响尚不清楚。在两名急性感染HIV-1的患者中，我们观察到在B*57限制的TW10表位（G9E）内出现了一个突变，该突变不能促进T细胞识别的强逃逸。这些患者携带的NK细胞受体KIR3DL1已知能识别HLA-B*5703，并与HIV-1的良好控制有关。因此，我们通过表面等离子体共振测试了G9E突变是否影响HLA-B*5703与可溶性KIR3DL1蛋白的结合，虽然识别了野生型序列和第二个（T3N）变体，但G9E变体取消了KIR3DL1的结合。我们扩展了这项研究，以确定KIR3DL1与携带TW10 C末端附近突变的表位和第二个HLA-B*57限制性表位IW9的相互作用的肽敏感性。一些氨基酸的变化干扰了KIR3DL1的结合，其中最极端的包括HLA-B*57通常选择的G9E突变。我们的研究结果表明，在HIV-1感染期间，一些早期出现的变异可能影响KIR-HLA相互作用，可能影响免疫识别。
Mutations within MHC class I-restricted epitopes have been studied in relation to T cell-mediated immune escape, but their impact on NK cells via interaction with killer Ig-like receptors (KIRs) during early HIV infection is poorly understood. In two patients acutely infected with HIV-1, we observed the appearance of a mutation within the B*57-restricted TW10 epitope (G9E) that did not facilitate strong escape from T cell recognition. The NK cell receptor KIR3DL1, carried by these patients, is known to recognize HLA-B*5703 and is associated with good control of HIV-1. Therefore, we tested whether the G9E mutation influenced the binding of HLA-B*5703 to soluble KIR3DL1 protein by surface plasmon resonance, and while the wild-type sequence and a second (T3N) variant were recognized, the G9E variant abrogated KIR3DL1 binding. We extended the study to determine the peptide sensitivity of KIR3DL1 interaction with epitopes carrying mutations near the C termini of TW10 and a second HLA-B*57-restricted epitope, IW9. Several amino acid changes interfered with KIR3DL1 binding, the most extreme of which included the G9E mutation commonly selected by HLA-B*57. Our results imply that during HIV-1 infection, some early-emerging variants could affect KIR-HLA interaction, with possible implications for immune recognition.