{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Leddy O"],"funding":["National Institute of Environmental Health Sciences","Center for Precision Cancer Medicine","NIAID NIH HHS","NIEHS NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["e84070"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10159623"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["CD8+ T cell recognition of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>)-specific peptides presented on major histocompatibility complex class I (MHC-I) contributes to immunity to tuberculosis (TB), but the principles that govern presentation of <i>Mtb</i> antigens on MHC-I are incompletely understood. In this study, mass spectrometry (MS) analysis of the MHC-I repertoire of <i>Mtb</i>-infected primary human macrophages reveals that substrates of <i>Mtb</i>'s type VII secretion systems (T7SS) are overrepresented among <i>Mtb</i>-derived peptides presented on MHC-I. Quantitative, targeted MS shows that ESX-1 activity is required for presentation of <i>Mtb</i> peptides derived from both ESX-1 substrates and ESX-5 substrates on MHC-I, consistent with a model in which proteins secreted by multiple T7SSs access a cytosolic antigen processing pathway via ESX-1-mediated phagosome permeabilization. Chemical inhibition of proteasome activity, lysosomal acidification, or cysteine cathepsin activity did not block presentation of <i>Mtb</i> antigens on MHC-I, suggesting involvement of other proteolytic pathways or redundancy among multiple pathways. Our study identifies <i>Mtb</i> antigens presented on MHC-I that could serve as targets for TB vaccines, and reveals how the activity of multiple T7SSs interacts to contribute to presentation of <i>Mtb</i> antigens on MHC-I."],"journal":["eLife"],"pubmed_title":["Immunopeptidomics reveals determinants of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; antigen presentation on MHC class I."],"pmcid":["PMC10159623"],"funding_grant_id":["R01 AI022553","R01 AI166313","R35 GM142900","P30 AI060354","R35GM142900-01","R01A1022553","P30 AI06035","P42 ES027707","T32 ES007020"],"pubmed_authors":["Bryson BD","White FM","Leddy O"],"additional_accession":[]},"is_claimable":false,"name":"Immunopeptidomics reveals determinants of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; antigen presentation on MHC class I.","description":"CD8+ T cell recognition of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>)-specific peptides presented on major histocompatibility complex class I (MHC-I) contributes to immunity to tuberculosis (TB), but the principles that govern presentation of <i>Mtb</i> antigens on MHC-I are incompletely understood. In this study, mass spectrometry (MS) analysis of the MHC-I repertoire of <i>Mtb</i>-infected primary human macrophages reveals that substrates of <i>Mtb</i>'s type VII secretion systems (T7SS) are overrepresented among <i>Mtb</i>-derived peptides presented on MHC-I. Quantitative, targeted MS shows that ESX-1 activity is required for presentation of <i>Mtb</i> peptides derived from both ESX-1 substrates and ESX-5 substrates on MHC-I, consistent with a model in which proteins secreted by multiple T7SSs access a cytosolic antigen processing pathway via ESX-1-mediated phagosome permeabilization. Chemical inhibition of proteasome activity, lysosomal acidification, or cysteine cathepsin activity did not block presentation of <i>Mtb</i> antigens on MHC-I, suggesting involvement of other proteolytic pathways or redundancy among multiple pathways. Our study identifies <i>Mtb</i> antigens presented on MHC-I that could serve as targets for TB vaccines, and reveals how the activity of multiple T7SSs interacts to contribute to presentation of <i>Mtb</i> antigens on MHC-I.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Apr","modification":"2026-06-02T21:54:14.424Z","creation":"2025-04-04T11:13:33.017Z"},"accession":"S-EPMC10159623","cross_references":{"pubmed":["37073954"],"doi":["10.7554/eLife.84070"]}}