Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS.
Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS.
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DOI：
10.1056/nejm200105313442203
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发表时间：
2001-05-31
影响因子：
158.5
通讯作者：
Carrington, M
中科院分区：
文献类型：
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作者：
Gao, XJ;Nelson, GW;Carrington, M
背景资料：从人类免疫缺陷病毒1型（HIV-1）感染到获得性免疫缺陷综合征（AIDS）的遗传多态性和进展速度的研究中，似乎最强的易感性是由主要组织相容性复合体（MHC）I类HLA-B*35，Cw*04等位基因赋予的。然而，已经观察到针对HLA-B*3501（最常见的HLA-B*35亚型）呈递的HIV-1表位的细胞毒性T淋巴细胞应答。我们检查了5个队列中的HLA-B*35亚型，并分析了HLA-B*35亚型之间的结构差异与进展为AIDS的风险之间的关系。方法：对850例血清转换和已知HIV-1感染日期的患者进行HLA I类基因位点的基因分型。生存分析相对于艾滋病的进展率进行，以确定密切相关的HLA-B*35亚型与不同的肽结合specificity.Results的影响：HLA-B*35亚型分为两组根据肽结合特异性：HLA-B*35-PY组，其主要由HLA-B*3501组成，并结合具有2位脯氨酸和9位酪氨酸的表位;以及更广泛反应性的HLA-B*35-Px基团，其也结合2位具有脯氨酸的表位，但可以结合9位的几种不同氨基酸（不包括酪氨酸）。HLA-B*35在加速进展到艾滋病的影响是完全归因于HLA-B*35-Px等位基因，其中一些不同的HLA-B*35-PY等位基因，只有一个氨基酸residues.Conclusions：这项分析表明，在HIV-1感染的患者中，HLA分子中的一个单一的氨基酸变化对进展到艾滋病的速度有很大的影响。HLA-B*35-PY和HLA-B*35-Px在疾病进展方面的不同结果突出了密切相关的I类分子的表位特异性在针对HIV-1的免疫防御中的重要性。（N Engl J Med 2001;344：1668-75.）版权所有（C）2001马萨诸塞州医学会。
Background: From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS.Methods: Genotyping of HLA class I loci was performed for 850 patients who seroconverted and had known dates of HIV-1 infection. Survival analyses with respect to the rate of progression to AIDS were performed to identify the effects of closely related HLA-B*35 subtypes with different peptide-binding specificities.Results: HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLA-B*3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (not including tyrosine) in position 9. The influence of HLA-B*35 in accelerating progression to AIDS was completely attributable to HLA-B*35-Px alleles, some of which differ from HLA-B*35-PY alleles by only one amino acid residue.Conclusions: This analysis shows that, in patients with HIV-1 infection, a single amino acid change in HLA molecules has a substantial effect on the rate of progression to AIDS. The different consequences of HLA-B*35-PY and HLA-B*35-Px in terms of disease progression highlight the importance of the epitope specificities of closely related class I molecules in the immune defense against HIV-1. (N Engl J Med 2001;344:1668-75.) Copyright (C) 2001 Massachusetts Medical Society.