{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:08:00Z","timestamp":1789157280218,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,5]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Dietary proteins induce antigen-specific immune responses, leading to oral tolerance or food allergies. While mouse models of allergic sensitization rely on antigen context and adjuvant signaling, exposure to purified proteins is usually sufficient for tolerance development in studies with soluble model antigens. In previous work, we discovered that the maize protein zein induces robust antigen-specific intestinal Tregs following normal chow exposure, but unexpectedly does not elicit a T cell response when delivered as a purified protein. Here, we investigated the mechanisms underlying these differential T cell responses, considering both biochemical properties of zein and its food matrix, as well as intestinal antigen processing. We focused on three zein preparations that induced different frequencies of antigen-specific intestinal T cells. While\n                  <jats:italic>in vitro<\/jats:italic>\n                  studies showed comparable presentation by dendritic cells,\n                  <jats:italic>in vivo<\/jats:italic>\n                  studies revealed stark differences in intestinal uptake. We identified differences in protein solubility and active sampling mechanisms as cooperative drivers of intestinal zein uptake. Different zein preparations could be sampled by either goblet cells, a route previously described for the model antigen OVA, or M cells, a route hypothesized for dietary proteins and established for transport of pathogenic bacteria. These findings also extend to peanuts, where the allergen Ara h 1 was selectively transported by goblet or M cells depending on food preparation, establishing examples of naturally occurring dietary M cell ligands. Finally, solubilizing zein increased intestinal uptake, and correspondingly feeding a diet with solubilized zein led to more intestinal zein-specific T cells compared to feeding the insoluble form. Overall, these findings suggest that intestinal uptake of dietary antigens is a regulated and context-dependent determinant of antigen-specific T cell induction, with implications for development of tolerance-restoring immunotherapies.\n                <\/jats:p>","DOI":"10.64898\/2026.09.01.748748","type":"posted-content","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T05:30:11Z","timestamp":1788672611000},"source":"Crossref","is-referenced-by-count":0,"title":["Intestinal uptake regulates T cell responses to dietary antigens"],"prefix":"10.64898","author":[{"given":"Ya-Ting","family":"Chang","sequence":"first","affiliation":[{"name":"NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA"},{"name":"Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry H.","family":"Le","sequence":"additional","affiliation":[{"name":"NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Morrison","sequence":"additional","affiliation":[{"name":"NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ell","family":"Schulman","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsui-Wen","family":"Chou","sequence":"additional","affiliation":[{"name":"NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie E.","family":"Blum","sequence":"additional","affiliation":[{"name":"NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA, USA"},{"name":"Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091112203351000_2026.09.01.748748v2.1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-018-8680-5"},{"key":"2026091112203351000_2026.09.01.748748v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.4"},{"key":"2026091112203351000_2026.09.01.748748v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.01.016"},{"key":"2026091112203351000_2026.09.01.748748v2.4","doi-asserted-by":"crossref","first-page":"e171241","DOI":"10.1172\/jci.insight.171241","article-title":"T follicular regulatory cells in food allergy promote IgE via IL-4","volume":"9","year":"2024","journal-title":"JCI Insight"},{"key":"2026091112203351000_2026.09.01.748748v2.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw6433"},{"key":"2026091112203351000_2026.09.01.748748v2.6","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8308-4"},{"key":"2026091112203351000_2026.09.01.748748v2.7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75660"},{"key":"2026091112203351000_2026.09.01.748748v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0461-z"},{"key":"2026091112203351000_2026.09.01.748748v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(94)90250-X"},{"key":"2026091112203351000_2026.09.01.748748v2.10","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.jaci.2011.06.007","article-title":"Allergic sensitization can be induced via multiple physiologic routes in an adjuvant-dependent manner","volume":"128","year":"2011","journal-title":"Journal of Allergy and Clinical Immunology"},{"key":"2026091112203351000_2026.09.01.748748v2.11","doi-asserted-by":"crossref","first-page":"357","DOI":"10.21037\/atm.2018.05.08","article-title":"Boiling and roasting treatment affecting the peanut allergenicity","volume":"6","year":"2018","journal-title":"Ann. 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