Toward a definition of self: Proteomic evaluation of the class I peptide repertoire
Toward a definition of self: Proteomic evaluation of the class I peptide repertoire
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DOI：
10.4049/jimmunol.172.5.2944
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Hildebrand, WH
中科院分区：
文献类型：
--
作者：
Hickman, HD;Luis, AD;Hildebrand, WH
MHC I类分子呈递宿主和病原体衍生的肽用于免疫监视。病毒和肿瘤非自身肽表位的研究受到了广泛关注，但问题仍然存在，“什么是自身？“对Edman基序和一小组单独肽的分析表明，I类自身库由数千种不同的肽组成。然而，这种自我肽背景并没有系统的特征，导致I类呈现自我的定义在很大程度上仍然是假设的。为了更好地理解由I类HLA取样的自身蛋白的宽度和性质，我们对来自人B细胞系的>200个内源性加载的HLA-B *1801肽进行测序。从肌动蛋白相关蛋白6到锌指蛋白147，肽源蛋白具有多种生物学和分子生物学功能。主要类别包括结合蛋白、催化蛋白和参与细胞代谢、生长和维持的蛋白。在遗传学上，呈现了由所有染色体编码的肽。由I类与人蛋白质组呈现的蛋白质的统计比较提供了经验证据，即由I类采样的蛋白质的范围是相对无偏的，除了在I类肽库中过度呈现的RNA结合蛋白质。这些数据表明，在该细胞系中，I类呈递的自身肽代表了细胞蛋白质组内容的全面和平衡的总结。重要的是，病毒和肿瘤诱导的几乎任何细胞区室或任何染色体的变化可以预期由I类分子呈递用于免疫识别。
MHC class I molecules present host- and pathogen-derived peptides for immune surveillance. Much attention is given to the search for viral and tumor nonself peptide epitopes, yet the question remains, "What is self?" Analyses of Edman motifs and of small sets of individual peptides suggest that the class I self repertoire consists of thousands of different peptides. However, there exists no systematic characterization of this self-peptide backdrop, causing the definition of class I-presented self to remain largely hypothetical. To better understand the breadth and nature of self proteins sampled by class I HLA, we sequenced >200 endogenously loaded HLA-B*1801 peptides from a human B cell line. Peptide-source proteins, ranging from actin-related protein 6 to zinc finger protein 147, possessed an assortment of biological and molecular functions. Major categories included binding proteins, catalytic proteins, and proteins involved in cell metabolism, growth, and maintenance. Genetically, peptides encoded by all chromosomes were presented. Statistical comparison of proteins presented by class I vs the human proteome provides empiric evidence that the range of proteins sampled by class I is relatively unbiased, with the exception of RNA-binding proteins that are over-represented in the class I peptide repertoire. These data show that, in this cell line, class I-presented self peptides represent a comprehensive and balanced summary of the proteomic content of the cell. Importantly, virus- and tumor-induced changes in virtually any cellular compartment or to any chromosome can be expected to be presented by class I molecules for immune recognition.