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

• DOI: 10.1016/j.isci.2022.103768
• Publication Date: 2022-01-18T01:53:17Z
• Authors: Peter Kubiniok; Ana Marcu; Leon Bichmann; Leon Kuchenbecker; Heiko Schuster; David J. Hamelin; Jérôme D. Duquette; Kevin A. Kovalchik; Laura Wessling; Oliver Kohlbacher; Hans-Georg Rammensee; Marian C. Neidert; Isabelle Sirois; Etienne Caron
• Keywords: Antigen processing

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.