The MHC I immunopeptidome conveys to the cell surface an integrative view of cellular regulation.
The MHC I immunopeptidome conveys to the cell surface an integrative view of cellular regulation.
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DOI：
10.1038/msb.2011.68
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发表时间：
2011-09-27
影响因子：
9.9
通讯作者：
Perreault, Claude
中科院分区：
文献类型：
--
作者：
Caron, Etienne;Vincent, Krystel;Fortier, Marie-Helene;Laverdure, Jean-Philippe;Bramoulle, Alexandre;Hardy, Marie-Pierre;Voisin, Gregory;Roux, Philippe P.;Lemieux, Sebastien;Thibault, Pierre;Perreault, Claude
自我/非自我的区分是生活的基本要求。由主要组织相容性复合物I类（MHC I）分子呈递的内源性肽代表了CD 8 T淋巴细胞自身的本质。这些MHC I肽（MIP）统称为免疫肽组。从系统水平的角度来看，对免疫肽组的起源、组成和可塑性知之甚少。在这里，我们表明，免疫肽组，因此，免疫自我的性质，是塑料和塑造细胞代谢活动。通过使用基于定量高通量质谱的方法，我们发现通过抑制雷帕霉素的哺乳动物靶点来改变细胞代谢会导致细胞表面MIP景观的动态变化。此外，我们提供了系统级的证据表明，免疫肽组项目在细胞表面的生化网络和代谢事件在细胞内的多个水平调节的代表。我们的发现为系统免疫学和预测生物学开辟了新的视角。事实上，预测免疫肽组响应细胞内在和外在因素的变化可能与免疫干预的合理设计有关。
Self/non-self discrimination is a fundamental requirement of life. Endogenous peptides presented by major histocompatibility complex class I (MHC I) molecules represent the essence of self for CD8 T lymphocytes. These MHC I peptides (MIPs) are collectively referred to as the immunopeptidome. From a systems-level perspective, very little is known about the origin, composition and plasticity of the immunopeptidome. Here, we show that the immunopeptidome, and therefore the nature of the immune self, is plastic and moulded by cellular metabolic activity. By using a quantitative high-throughput mass spectrometry-based approach, we found that altering cellular metabolism via the inhibition of the mammalian target of rapamycin results in dynamic changes in the cell surface MIPs landscape. Moreover, we provide systems-level evidence that the immunopeptidome projects at the cell surface a representation of biochemical networks and metabolic events regulated at multiple levels inside the cell. Our findings open up new perspectives in systems immunology and predictive biology. Indeed, predicting variations in the immunopeptidome in response to cell-intrinsic and -extrinsic factors could be relevant to the rational design of immunotherapeutic interventions.
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