{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:16:04Z","timestamp":1786115764360,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,4]]},"group-title":"Immunology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["1R21CA293614-01A1"],"award-info":[{"award-number":["1R21CA293614-01A1"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014185","name":"Searle Scholars Program","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014185","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01gd7b947","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Upon skin colonization, the prevalent human skin commensal\n                  <jats:italic>S. epidermidis<\/jats:italic>\n                  can elicit a CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell response that protects against pathogens or clears tumors. The microbial features that drive this response are undefined, limiting our ability to understand and predict commensal-immune crosstalk and to engineer potent commensal-derived immunotherapies. To uncover these microbial features, we harnessed both the natural variation in CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell induction across primary human isolates of\n                  <jats:italic>Staphylococcus<\/jats:italic>\n                  and our ability to genetically manipulate these strains. Stimulatory strains exhibit increased quorum sensing activation, which turns on a unique commensal-associated gene family, called phenol-soluble modulin \u03b5 (PSM\u03b5), that is required for CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell activation. PSM\u03b5 not only acts as the immunodominant CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell antigen but also enhances cross-presentation in an antigen-agnostic manner. Co-delivering PSM\u03b5 promotes CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell priming to an exogenous antigen via a mechanism that is independent of formyl peptide receptor and co-stimulatory receptor upregulation. Thus, we demonstrate that specific aspects of microbiome-immune crosstalk can be distilled to molecular components, which engage in previously undescribed mechanisms and can be harnessed for immunotherapy without requiring live bacterial colonization.\n                <\/jats:p>","DOI":"10.64898\/2026.07.30.741773","type":"posted-content","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:05:26Z","timestamp":1785895526000},"source":"Crossref","is-referenced-by-count":0,"title":["PSM\u03b5 controls skin commensal CD8\n                  <sup>+<\/sup>\n                  T cell activation"],"prefix":"10.64898","author":[{"given":"William S.","family":"Owens","sequence":"first","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Lenzi","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Hurd","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie J. Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Staudinger","sequence":"additional","affiliation":[{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Berdy","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Lian","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namrata D.","family":"Udeshi","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Carr","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Johnston","sequence":"additional","affiliation":[{"name":"MD Anderson, Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Livny","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-1402","authenticated-orcid":false,"given":"Y. 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