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In this study, mass spectrometry (MS) analysis of the MHC-I repertoire of\n                    <jats:italic>Mtb<\/jats:italic>\n                    -infected primary human macrophages reveals that substrates of\n                    <jats:italic>Mtb<\/jats:italic>\n                    \u2019s type VII secretion systems (T7SS) are overrepresented among\n                    <jats:italic>Mtb<\/jats:italic>\n                    -derived peptides presented on MHC-I. Quantitative, targeted MS shows that ESX-1 activity is required for presentation of\n                    <jats:italic>Mtb<\/jats:italic>\n                    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\n                    <jats:italic>Mtb<\/jats:italic>\n                    antigens on MHC-I, suggesting involvement of other proteolytic pathways or redundancy among multiple pathways. Our study identifies\n                    <jats:italic>Mtb<\/jats:italic>\n                    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\n                    <jats:italic>Mtb<\/jats:italic>\n                    antigens on MHC-I.\n                  <\/jats:p>","DOI":"10.7554\/elife.84070","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T08:00:25Z","timestamp":1681891225000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.84070","source":"Crossref","is-referenced-by-count":61,"title":["Immunopeptidomics reveals determinants of Mycobacterium tuberculosis antigen presentation on MHC class I"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3437-1956","authenticated-orcid":true,"given":"Owen","family":"Leddy","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Engineering, Massachusetts Institute of Technology","place":["Cambridge, United States"]},{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"Ragon Institute of Massachusetts General Hospital, Harvard, and MIT","place":["Cambridge, United States"]},{"name":"Koch Institute for Integrative Cancer Research","place":["Cambridge, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-1651","authenticated-orcid":true,"given":"Forest M","family":"White","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Engineering, Massachusetts Institute of Technology","place":["Cambridge, United States"]},{"name":"Koch Institute for Integrative Cancer Research","place":["Cambridge, United States"]},{"name":"Center for Precision Cancer Medicine","place":["Cambridge, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1716-6712","authenticated-orcid":true,"given":"Bryan D","family":"Bryson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biological Engineering, Massachusetts Institute of Technology","place":["Cambridge, United States"]},{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"Ragon Institute of Massachusetts General Hospital, Harvard, and MIT","place":["Cambridge, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1111\/j.1365-2958.2006.05409.x","type":"journal-article","article-title":"A specific secretion system mediates PPE41 transport in pathogenic mycobacteria","volume":"62","author":"Abdallah","year":"2006","journal-title":"Molecular Microbiology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nrmicro1773","type":"journal-article","article-title":"Type VII secretion -- mycobacteria show the way","volume":"5","author":"Abdallah","year":"2007","journal-title":"Nature Reviews. 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