Abstract
The large array of peptides presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules is referred to as the MHC class I immunopeptidome. Although the MHC class I immunopeptidome is ubiquitous in mammals and represents a critical component of the immune system, very little is known, in any species, about its composition across most tissues and organs in vivo. We applied mass spectrometry (MS) technologies to draft the first tissue-based atlas of the murine MHC class I immunopeptidome in health. Peptides were extracted from 19 normal tissues from C57BL/6 mice and prepared for MS injections, resulting in a total number of 28,448 high-confidence H2Db/Kb-associated peptides identified and annotated in the atlas. This atlas provides initial qualitative data to explore the tissue-specificity of the immunopeptidome and serves as a guide to identify potential tumor-associated antigens from various cancer models. Our data were shared via PRIDE (PXD008733), SysteMHC Atlas (SYSMHC00018) and SWATH Atlas. We anticipate that this unique dataset will be expanded in the future and will find wide applications in basic and translational immunology.
Highlights
Background & SummaryT cells are an essential cell type for next-generation vaccines and immunotherapies[1]
T cells recognize antigens in the form of short peptides presented by major histocompatibility complex (MHC) molecules — collectively referred to as the MHC ligandome/peptidome or immunopeptidome[2,3,4]
The cellular immunopeptidome is composed of thousands of MHC-associated peptides—each peptide ranging in abundance between approximately 1 and 10,000 copies per cell[6]
Summary
T cells are an essential cell type for next-generation vaccines and immunotherapies[1]. Given the advances in MS technology over the last decade, the availability of protocols for the isolation MHC-associated peptides from multiple species and tissue types, and the relatively less complex composition of the immunopeptidome in mouse models (in comparison with humans), we reasoned that the time was ripe to initiate a systematic effort to draft the first MS-based atlas of the murine MHC class I immunopeptidome in health using a commonly used mouse strain. To this end, we used data-dependent acquisition (DDA) MS to generate immunopeptidomic data from 19 tissues of healthy C57BL/6 mice. This reference map, together with its connection with SWATH Atlas, lays down the foundation to perform robust quantitative analysis of the murine immunopeptidome using next-generation SWATH/Data-independent acquisition (DIA)-MS technologies[26,33]
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