School of Public Health, University of California, Berkeley, CA, USA.
Trends Genet. 2012 Oct;28(10):480-6. doi: 10.1016/j.tig.2012.06.007. Epub 2012 Aug 3.
Highly polymorphic exons of the major histocompatibility complex (MHC, or HLA in humans) encode critical amino acids that bind foreign peptides. Recognition of the peptide-MHC complexes by T cells initiates the adaptive immune response. The particular structure of these exons facilitates gene conversion(GC) events, leading to the generation of new alleles. Estimates for allele creation and loss indicate that more than 10000 such alleles are circulating at low frequencies in human populations. Empirical sampling has affirmed this expectation. This suggests that the MHC loci have a system for moving valuable and often complex variants into adaptive service. Here, we argue that HLA loci carry many new mutant alleles prepared to assume epidemiologically meaningful roles when called on by selection provoked by exposure to new and evolving pathogens. Because new mutant alleles appear in a population at the lowest possible frequency (i.e., a single copy), they have typically been thought of as having little consequence. However, this large population of rare yet potentially valuable new alleles may contribute to pathogen defense.
高度多态性的主要组织相容性复合体 (MHC，或人类中的 HLA) 外显子编码与外来肽结合的关键氨基酸。T 细胞对肽-MHC 复合物的识别启动了适应性免疫反应。这些外显子的特殊结构促进了基因转换 (GC) 事件，导致新等位基因的产生。等位基因产生和丢失的估计表明，在人类群体中，有超过 10000 个这样的等位基因以低频率循环。实证抽样证实了这一预期。这表明 MHC 基因座具有一种将有价值且通常复杂的变体转移到适应性服务中的系统。在这里，我们认为 HLA 基因座携带许多新的突变等位基因，当受到新出现和不断进化的病原体暴露引发的选择的影响时，这些等位基因准备承担具有流行病学意义的作用。由于新的突变等位基因以最低可能的频率（即单拷贝）出现在人群中，因此它们通常被认为影响不大。然而，这种大量的稀有但潜在有价值的新等位基因可能有助于病原体防御。
