{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:02:45Z","timestamp":1756252965975,"version":"3.44.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1-INO-2023-1341-A-N"],"award-info":[{"award-number":["1-INO-2023-1341-A-N"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000901","name":"Juvenile Diabetes Research Foundation International","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The interactions between endogenous retroviruses (ERVs) and major histocompatibility complex molecules may significantly influence autoimmune diseases due to their common roles in the evolution and development of the adaptive immune system. Notably, regions within the Gag antigens of a specific group of ERVs, similar to murine leukemia retroviruses, exhibit patterns of sequence conservation, variation, and mutation. One highly conserved peptide of Gag, p5-13 (VTTPLSLTL), binds with high affinity to a nonclassic major histocompatibility complex molecule, Qa-1, and is preferentially recognized by T cells enriched in the pancreas of nonobese diabetic (NOD) mice, which spontaneously develop autoimmune type 1 diabetes. Interestingly, deep sequencing analysis of the Gag genes expressed in NOD mice has revealed numerous mutations flanking the conserved Qa-1\u2013binding sequences. This includes 1 epitope, p310-328, which contains both conserved and mutated residues that can elicit autoreactive T cells in NOD mice. A specific residue, D316, within this epitope accumulates multiple mutations as the disease progresses, leading to a reduction in the consensus score in sequence alignment at this position during the later stages of prediabetes. Consistently, the substitution of the D316 residue with a dominant mutant, G316, enhances the antigenicity of this epitope, stimulating autoreactive T cells in prediabetic NOD mice to release interferon-\u03b3 . Thus, sequence variants of ERV Gag antigens encode overlapping conserved and highly mutated epitopes that can be recognized by T cells and utilized for biomarker discovery.<\/jats:p>","DOI":"10.1093\/immhor\/vlaf033","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T23:50:00Z","timestamp":1756165800000},"source":"Crossref","is-referenced-by-count":0,"title":["Identification of conserved T cell epitopes and flanking amino acid mutants of endogenous retrovirus Gag antigen in nonobese diabetic mice"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4040-5048","authenticated-orcid":false,"given":"Yang D","family":"Dai","sequence":"first","affiliation":[{"name":"HERV Laboratory , San Diego, CA,","place":["United States"]},{"name":"Biomedical Research Institute of Southern California , Oceanside, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhui","family":"Li","sequence":"additional","affiliation":[{"name":"Biosettia Inc. , San Diego, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Margosiak","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute of Southern California , Oceanside, CA,","place":["United States"]},{"name":"Biosettia Inc. , San Diego, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Yuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Biosettia Inc. , San Diego, CA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"2025082519495124200_vlaf033-B1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1146\/annurev.iy.08.040190.002401","article-title":"Host genetic control of spontaneous and induced immunity to Friend murine retrovirus infection","volume":"8","author":"Chesebro","year":"1990","journal-title":"Annu Rev Immunol"},{"key":"2025082519495124200_vlaf033-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.immunol.18.1.1","article-title":"Discovering the role of the major histocompatibility complex in the immune response","volume":"18","author":"McDevitt","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"2025082519495124200_vlaf033-B3","doi-asserted-by":"crossref","first-page":"8289","DOI":"10.1128\/JVI.72.10.8289-8300.1998","article-title":"Structure and distribution of endogenous nonecotropic murine leukemia viruses in wild mice","volume":"72","author":"Tomonaga","year":"1998","journal-title":"J Virol"},{"key":"2025082519495124200_vlaf033-B4","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1128\/JVI.01926-08","article-title":"Mobilization of endogenous retroviruses in mice after infection with an exogenous retrovirus","volume":"83","author":"Evans","year":"2009","journal-title":"J Virol"},{"key":"2025082519495124200_vlaf033-B5","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nri.2016.27","article-title":"Immune responses to endogenous retroelements: taking the bad with the good","volume":"16","author":"Kassiotis","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"2025082519495124200_vlaf033-B6","doi-asserted-by":"crossref","first-page":"852","DOI":"10.2337\/diabetes.53.3.852","article-title":"Association of human endogenous retrovirus K-18 polymorphisms with type 1 diabetes","volume":"53","author":"Marguerat","year":"2004","journal-title":"Diabetes"},{"key":"2025082519495124200_vlaf033-B7","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1038\/s41467-024-45201-6","article-title":"T-bet(+) B cells are activated by and control endogenous retroviruses through TLR-dependent mechanisms","volume":"15","author":"Rauch","year":"2024","journal-title":"Nat Commun"},{"key":"2025082519495124200_vlaf033-B8","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1126\/science.346.6216.1486","article-title":"MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses","volume":"346","author":"Zeng","year":"2014","journal-title":"Science"},{"key":"2025082519495124200_vlaf033-B9","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/imr.13378","article-title":"Antibodies against endogenous retroviruses","volume":"328","author":"Chisca","year":"2024","journal-title":"Immunol Rev"},{"key":"2025082519495124200_vlaf033-B10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1600-065X.1993.tb01531.x","article-title":"The bacterial and mouse mammary tumor virus superantigens; 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