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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:p>\n                    We compared duodenal biopsies showing active celiac disease (CeD) to normal controls using single-cell RNA sequencing, cyclic immunofluorescence, RNAScope, and proximity ligation assays. There is increased infiltration of villous but not crypt epithelium T cells bearing either \u03b1\u03b2 or \u03b3\u03b4 T cell receptors (TCRs) in CeD. Both T cell subsets are activated cytotoxic T lymphocytes (CTLs) and are the predominant mucosal source of IFN\u03b3. In response to this IFN\u03b3, villous but not crypt enterocytes show an IFN\u03b3 signature, including nuclear phospho-STAT1 protein, class II HLA molecules and IFN\u03b3-inducible chemokines known to recruit CTLs (e.g., CCL3, CCL4, CXCL10, and CXCL11) and receptors for these chemokines are expressed on the infiltrating CTLs. Villous enterocytes also display increased HLA-E and HLA-B mRNAs and proteins. Bioinformatic analyses (NICHES) and proximity ligation assays show frequent binding of both \u03b1\u03b2 and \u03b3\u03b4 TCRs with enterocyte\n                    <jats:italic toggle=\"yes\">HLA-E<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">HLA-B<\/jats:italic>\n                    , but not\n                    <jats:italic toggle=\"yes\">HLA-DR<\/jats:italic>\n                    . In contrast, NKG2C, proposed as an alternative trigger of CTL activation, is infrequently expressed and shows few interactions with HLA-E. Our data suggest that activated intraepithelial CTLs produce IFN\u03b3 which recruits additional CTLs and increases antigen-dependent killing of villous epithelium using either conventional or HLA-E antigen presentation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2525433123","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T19:09:38Z","timestamp":1770318578000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["T cell receptors for antigen on intraepithelial cytolytic T lymphocytes in celiac disease engage enterocyte HLA-E and HLA-B"],"prefix":"10.1073","volume":"123","author":[{"given":"Justin E.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New 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