Motif inference reveals optimal CTL epitopes presented by HLA class I alleles highly prevalent in Southern Africa
Motif inference reveals optimal CTL epitopes presented by HLA class I alleles highly prevalent in Southern Africa
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DOI：
10.4049/jimmunol.176.8.4699
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发表时间：
2006-04-15
影响因子：
4.4
通讯作者：
Goulder, Philip J. R.
中科院分区：
文献类型：
--
作者：
Honeyborne, Isobella;Rathod, Almas;Goulder, Philip J. R.
HIV特异性CTL在HIV免疫控制中发挥核心作用。了解这种免疫反应的成功或失败的基础需要鉴定CTL靶向的特定表位。然而，在受全球流行病影响最严重的人群中，由于缺乏对这些人群中高度流行的许多HLA I类等位基因的特征描述，这种基本知识受到阻碍。总的来说，已经确定了一小部分（9%）HLA I类等位基因的肽结合基序，这些等位基因在高加索人群中普遍存在。因此，这些研究开始定义；在疫情中心的南非祖鲁/科萨人群中，等位基因所呈现的表位高度普遍，但其肽结合基序尚未表征。利用基序推断方法，对南非德班祖鲁/科萨人群中普遍存在的4个等位基因B*3916、B*4201、B*8101和Cw*1801的表位进行了描述。重要的是，这种方法还可以在某些情况下促进表位的优化，在这些情况下，文献中存在关于肽结合基序的相互矛盾的报道，例如HLA-A*2902，在南部非洲人群中也非常普遍。这些数据表明，先前HLA-A*2902在HLA-A等位基因中位于任何已知的HLA-A超型之外的异常位置是人为的，A*2902基序的真实位置与A1和A24超型重叠。
HIV-specific CTL play a central role in immune control of HIV. The basis for understanding the success or failure of this immune response requires identification of the specific epitopes targeted by CTL. However, in populations most severely affected by the global epidemic, this fundamental knowledge is hindered by the lack of characterization of many of the HLA class I alleles highly prevalent in such populations. Overall, the peptide-binding motif has been determined for a small minority (9%) of HLA class I alleles, with a strong bias toward those alleles prevalent in Caucasoid populations. These studies therefore set out to define; in a South African Zulu/Xhosa population at the epicenter of the epidemic, the epitopes presented by alleles highly prevalent, but for which the peptide-binding motif had not been characterized. Using a method of motif inference, epitopes presented by four such alleles prevalent in the Zulu/Xhosa population of Durban, South Africa, namely, B*3916, B*4201, B*8101, and Cw*1801, are described. Importantly, this approach may additionally facilitate optimization of epitopes in certain instances where conflicting reports in the literature exist regarding the peptide-binding motif, such as for HLA-A*2902, also highly prevalent in southern African populations. These data indicate that the previously anomalous position of HLA-A*2902 among HLA-A alleles, outside any recognized HLA-A supertype, is artifactual, and the true position of the A*2902 motif overlaps those of the A1 and A24 supertypes.