Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules.
Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules.
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DOI：
10.1002/prca.201500106
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Joyce S
中科院分区：
文献类型：
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作者：
Spencer CT;Bezbradica JS;Ramos MG;Arico CD;Conant SB;Gilchuk P;Gray JJ;Zheng M;Niu X;Hildebrand W;Link AJ;Joyce S
肽的MHC I类呈递允许T细胞调查宿主细胞的胞质蛋白环境。在感染期间，自身肽的呈递部分地被微生物肽的呈递所取代。然而，很少有人知道在感染过程中提出的自我肽，尽管微生物感染改变宿主细胞基因表达模式和蛋白质代谢。在牛痘病毒感染前后，通过质谱法测定由HLA-A*01;01，-A*02;01，-B*07;02，-B*35;01和-B*45;01呈递的自身肽库。我们观察到自身肽库发生了深刻的变化，感染后独特地呈现了数百种自身肽，我们为此创造了“自身肽组变化”一词。感染后呈现的新型自身肽的分数对于不同的HLA I类分子而变化。大部分（~40%）的自身肽组移位由来自I型干扰素诱导基因的肽组成，与病毒感染的细胞反应一致。有趣的是，当对约300个人类基因组进行搜索时，感染后呈现的约12%的自身肽显示等位基因变异。临床移植环境中的自身肽组移位可能通过在感染诱导的炎症背景下呈递新的自身肽而导致同种异体反应性。
MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism. The self peptide repertoire presented by HLA-A*01;01, -A*02;01, -B*07;02, -B*35;01 and -B*45;01 was determined by mass spectrometry before and after vaccinia virus infection. We observed a profound alteration in the self peptide repertoire with hundreds of self peptides uniquely presented after infection for which we have coined the term ‘self peptidome shift’. The fraction of novel self peptides presented following infection varied for different HLA class I molecules. A large part (~40%) of the self peptidome shift was composed of peptides derived from type I interferon-inducible genes, consistent with cellular responses to viral infection. Interestingly, ~12% of self peptides presented after infection showed allelic variation when searched against ~300 human genomes. Self peptidome shift in a clinical transplant setting could result in alloreactivity by presenting new self peptides in context of infection-induced inflammation.