Understanding the constitutive presentation of MHC class I immunopeptidomes in 
primary tissues

Kubiniok, P; Marcu, A; Bichmann, L; Kuchenbecker, L; Schuster, H; Hamelin, DJ; Duquette, JD; Kovalchik, KA; Wessling, L; Kohlbacher, O; Rammensee, H-G; Neidert, MC; Sirois, I; Caron, E

doi:10.1016/j.isci.2022.103768

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Understanding the constitutive presentation of MHC class I immunopeptidomes in primary tissues

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Kohlbacher, O
Research Group Biomolecular Interactions, Max Planck Institute for Developmental Biology, Max Planck Society;

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Citation

Kubiniok, P., Marcu, A., Bichmann, L., Kuchenbecker, L., Schuster, H., Hamelin, D., et al. (2022). Understanding the constitutive presentation of MHC class I immunopeptidomes in primary tissues. iScience, 25(2): 103768. doi:10.1016/j.isci.2022.103768.

Cite as: https://hdl.handle.net/21.11116/0000-000A-3784-3

Abstract

Understanding 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 contexts in 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 presentation in vivo across mammalian species.