Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding
Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding
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DOI：
10.7554/elife.05345
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发表时间：
2015-04-10
期刊：
影响因子：
7.7
通讯作者：
Kaufman, Jim
中科院分区：
文献类型：
--
作者：
Chappell, Paul;Meziane, El Kahina;Kaufman, Jim
高度多态的主要组织相容性复合体（MHC）分子是适应性免疫反应的核心，在多种疾病和疫苗接种中起着至关重要的作用。我们报道，在鸡和人类中，肽呈现的宽度和I类分子的细胞表面表达水平呈负相关。这种关系与对传染性病原体的保护性反应有关，包括导致鸡致死性肿瘤的马立克病病毒和人类免疫缺陷病毒感染进展为人类艾滋病。我们提出肽结合库的差异定义了MHC I类分子的两组策略进化为通才和专才，以适应不同的病原体抗性模式。我们认为细胞表面表达水平的差异确保了最佳外周T细胞反应的发展。肽库和表达的反比关系显然是MHC分子的基本特性，其影响从免疫学和医学延伸到进化生物学和保护。
Highly polymorphic major histocompatibility complex (MHC) molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and human immunodeficiency virus infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation.