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The enzyme \u03b3-interferon-inducible lysosomal thiol reductase (GILT) is expressed constitutively in lysosomes of antigen presenting cells and reproductive tract epithelial cells. GILT catalyzes disulfide bond reduction during protein degradation that generates T cell epitopes. To evaluate the role that GILT plays in chlamydial infections, C57BL\/6 WT mice and mice deficient in Ifi30 (GILT-KO) were challenged vaginally with Chlamydia muridarum (Cm). Both were equally susceptible to the Cm infection and upper genital tract pathology. To assess GILT\u2019s role in processing MOMP epitopes, WT and GILT-KO mice were immunized with native (nMOMP) or recombinant (rMOMP) antigens. In both strains vaccination with Cm\u2002nMOMP and rMOMP induced a similar spectrum of MOMP-specific antibodies. nMOMP immunization generated higher neutralizing antibody titers than rMOMP, but neutralizing titers did not differ between mouse strains. Splenocytes from vaccinated WT and GILT-KO mice recognized T cell epitopes in nMOMP, and to a lesser extent with rMOMP. No protection was seen in either WT or GILT-KO mice vaccinated with rMOMP based on intensity and duration of vaginal shedding, upper genital tract pathology, and fertility post-infection. nMOMP vaccination protected WT mice based on attenuated bacterial shedding and preserved fertility but nMOMP-vaccinated GILT-KO mice were not protected. The failure of nMOMP vaccination in GILT-KO mice revealed that GILT-dependent MOMP epitope processing was outcome determinative and identified a pan-serovar, likely protective, class II T cell epitope in MOMP constant domain 3.<\/jats:p>","DOI":"10.1093\/immhor\/vlag018","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T02:28:11Z","timestamp":1776306491000},"source":"Crossref","is-referenced-by-count":0,"title":["Presentation of the protective epitope in a\n                    <i>Chlamydia muridarum<\/i>\n                    MOMP vaccine is dependent on \u03b3-interferon-inducible lysosomal thiol reductase (GILT)"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-5121","authenticated-orcid":false,"given":"Sukumar","family":"Pal","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine , Irvine, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond M","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale University School of Medicine , New Haven, CT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delia F","family":"Tifrea","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine , Irvine, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cresswell","sequence":"additional","affiliation":[{"name":"Departments of Immunobiology and Cell Biology, Yale University School of Medicine , New Haven, CT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M","family":"de la Maza","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine , Irvine, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"2026110311230138900_vlag018-B1","doi-asserted-by":"crossref","first-page":"e1544","DOI":"10.1016\/S2214-109X(24)00266-3","article-title":"WHO global research priorities for sexually transmitted infections","volume":"12","author":"Gottlieb","year":"2024","journal-title":"Lancet Glob Health"},{"key":"2026110311230138900_vlag018-B2","author":"CDC","year":"2024"},{"key":"2026110311230138900_vlag018-B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta20220","article-title":"The natural history of Chlamydia trachomatis infection in women: a multi-parameter evidence synthesis","volume":"20","author":"Price","year":"2016","journal-title":"Health Technol Assess"},{"key":"2026110311230138900_vlag018-B4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/00007435-199207000-00001","article-title":"Pelvic inflammatory disease and fertility. 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