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标题：Understanding the constitutive presentation of MHC class I immunopeptidomes in primary tissues
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作者：Peter Kubiniok ; Ana Marcu ; Leon Bichmann 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：2
页码：1-24
DOI：10.1016/j.isci.2022.103768
语种：English
出版社：Elsevier
摘要：SummaryUnderstanding the molecular principles that govern the composition of the MHC-I immunopeptidome across different primary tissues is fundamentally important to predict how T cells respond in different contextsin vivo. Here, we performed a global analysis of the MHC-I immunopeptidome from 29 to 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, HLA-B, and HLA-C allotypes do not contribute evenly to the global composition of the MHC-I immunopeptidome across multiple human tissues. Second, we found that tissue-specific and housekeeping MHC-I peptides share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-I immunopeptidome at the organism-wide scale. Fourth, we uncovered new components of the antigen processing and presentation network, including the carboxypeptidases CPE, CNDP1/2, and CPVL. Together, this study opens up new avenues toward a system-wide understanding of antigen presentationin vivoacross mammalian species.Graphical abstractDisplay OmittedHighlights•Tissue-specific and housekeeping MHC class I peptides share distinct properties•HLA-A, HLA-B, and HLA-C allotypes contribute very unevenly to the pool of class I peptides•MHC-I immunopeptidomes are represented by evolutionarily conserved proteins•An extended antigen processing and presentation pathway is uncoveredBiological sciences; Biomolecules; Immunology; Peptides