HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection.
HLA class I molecular variation and peptide-binding properties suggest a model of joint divergent asymmetric selection.
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DOI：
10.1007/s00251-016-0918-x
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发表时间：
2016-07
期刊：
影响因子：
3.2
通讯作者：
Sanchez-Mazas A
中科院分区：
文献类型：
--
作者：
Buhler S;Nunes JM;Sanchez-Mazas A
HLA I类分子的主要功能是向细胞毒性T淋巴细胞呈递病原体衍生肽。这一功能被认为驱动了每个HLA位点异常多态的维持，为杂合子个体提供了免疫优势，能够呈现比纯合子更大的肽库。然而，这似乎是矛盾的，在一些孤立的人群中，单个HLA位点的多样性降低了。这项研究表明，在46个人群中，同时考虑的两个HLA-A和HLA-B基因的预测功能多样性水平是相似的（几乎不变），即使每个位点的多样性都有所降低。因此，我们提出HLA-A和HLA-B通过联合发散不对称选择模型进化，赋予所有群体同等的免疫潜力。观察到的HLA-C的独特模式可以通过其向杀伤细胞免疫球蛋白样受体（KIR）活性调节的功能进化而不是肽呈现来解释。本文的在线版本（doi:10.1007/s00251-016-0918-x）包含补充材料，可供授权用户使用。
The main function of HLA class I molecules is to present pathogen-derived peptides to cytotoxic T lymphocytes. This function is assumed to drive the maintenance of an extraordinary amount of polymorphism at each HLA locus, providing an immune advantage to heterozygote individuals capable to present larger repertories of peptides than homozygotes. This seems contradictory, however, with a reduced diversity at individual HLA loci exhibited by some isolated populations. This study shows that the level of functional diversity predicted for the two HLA-A and HLA-B genes considered simultaneously is similar (almost invariant) between 46 human populations, even when a reduced diversity exists at each locus. We thus propose that HLA-A and HLA-B evolved through a model of joint divergent asymmetric selection conferring all populations an equivalent immune potential. The distinct pattern observed for HLA-C is explained by its functional evolution towards killer cell immunoglobulin-like receptor (KIR) activity regulation rather than peptide presentation. The online version of this article (doi:10.1007/s00251-016-0918-x) contains supplementary material, which is available to authorized users.