Extensive HLA class I allele promiscuity among viral CTL epitopes

Extensive HLA class I allele promiscuity among viral CTL epitopes
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DOI:
10.1002/eji.200737365
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发表时间:
2007-09-01
影响因子:
5.4
通讯作者:
Brander, Christian
Brander, Christian
中科院分区:
医学3区
文献类型:
--
作者:
Frahm, Nicole;Yusim, Karina;Brander, Christian

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辅助性T表位与MHC 11类分子的混杂结合已经得到了很好的证实,但存在混杂的i类限制性表位的例子很少。为了解决HLA I类肽混杂的程度,在100名受试者中测试了242个明确定义的病毒表位的反应,而不考虑个体的HLA类型。令人惊讶的是,在所有检测到的应答中,有一半是在缺乏最初报道的限制性HLA I类等位基因的情况下发现的,只有3%的表位在其原始等位基因存在时被完全识别。功能分析证实了HLA I类限制性T细胞表位在HLA I类超型和编码在不同I类位点上的几个替代等位基因上的频繁识别。这些数据对理解MHC i类限制性抗原呈递和疫苗开发具有重要意义。
Promiscuous binding of T helper epitopes to MHC class 11 molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development.