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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,12,5]]},"abstract":"<jats:p>\n                    In both humans and NOD mice, type 1 diabetes (T1D) develops from the autoimmune destruction of pancreatic beta cells by T cells. Interactions between both helper CD4\n                    <jats:sup>+<\/jats:sup>\n                    and cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells are essential for T1D development in NOD mice. Previous work has indicated that pathogenic T cells arise from deleterious interactions between relatively common genes which regulate aspects of T cell activation\/effector function (\n                    <jats:italic>Ctla4, Tnfrsf9,<\/jats:italic>\n                    <jats:italic>Il2\/Il21<\/jats:italic>\n                    ), peptide presentation (\n                    <jats:italic>\n                      H2-A\n                      <jats:sup>\u2009g7<\/jats:sup>\n                    <\/jats:italic>\n                    ,\n                    <jats:italic>B2m<\/jats:italic>\n                    ), and T cell receptor (TCR) signaling (\n                    <jats:italic>Ptpn22<\/jats:italic>\n                    ). Here, we used a combination of subcongenic mapping and a CRISPR\/Cas9 screen to identify the NOD-encoded mammary tumor virus (\n                    <jats:italic>Mtv<\/jats:italic>\n                    )3 provirus as a genetic element affecting CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell interactions through an additional mechanism, altering the TCR repertoire.\n                    <jats:italic>Mtv3<\/jats:italic>\n                    encodes a superantigen (SAg) that deletes the majority of V\u03b23\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes in NOD mice. Ablating\n                    <jats:italic>Mtv3<\/jats:italic>\n                    and restoring V\u03b23\n                    <jats:sup>+<\/jats:sup>\n                    T cells has no effect on spontaneous T1D development in NOD mice. However, transferring\n                    <jats:italic>Mtv3<\/jats:italic>\n                    to C57BL\/6 (B6) mice congenic for the NOD\n                    <jats:italic>\n                      H2\n                      <jats:sup>\u2009g7<\/jats:sup>\n                    <\/jats:italic>\n                    MHC haplotype (B6.\n                    <jats:italic>\n                      H2\n                      <jats:sup>\u2009g7<\/jats:sup>\n                    <\/jats:italic>\n                    ) completely blocks their normal susceptibility to T1D mediated by transferred CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells transgenically expressing AI4 or NY8.3 TCRs. The entire genetic effect is manifested by V\u03b23\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which unless deleted by\n                    <jats:italic>Mtv3<\/jats:italic>\n                    , accumulate in insulitic lesions triggering in B6 background mice the pathogenic activation of diabetogenic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Our findings provide evidence that endogenous\n                    <jats:italic>Mtv<\/jats:italic>\n                    SAgs can influence autoimmune responses. Furthermore, since most common mouse strains have gaps in their TCR V\u03b2 repertoire due to\n                    <jats:italic>Mtvs<\/jats:italic>\n                    , it raises questions about the role of\n                    <jats:italic>Mtvs<\/jats:italic>\n                    in other mouse models designed to reflect human immune disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2312039120","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T13:35:15Z","timestamp":1701178515000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Deletion of V\u03b23\n                    <sup>+<\/sup>\n                    CD4\n                    <sup>+<\/sup>\n                    T cells by endogenous mouse mammary tumor virus 3 prevents type 1 diabetes induction by autoreactive CD8\n                    <sup>+<\/sup>\n                    T cells"],"prefix":"10.1073","volume":"120","author":[{"given":"Cheng","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Animal Sciences, University of Florida, Gainesville, FL 32611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadie A.","family":"Clements","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 65201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Gu","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 65201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron M.","family":"Geurts","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton E.","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-5925","authenticated-orcid":false,"given":"David. V.","family":"Serreze","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Guang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-3335","authenticated-orcid":false,"given":"John P.","family":"Driver","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia, MO 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Ono, Molecular biology of type A endogenous retrovirus. Kitasato Arch. Exp. Med. 63, 77\u201390 (1990).","journal-title":"Kitasato Arch. Exp. Med."},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.4.1203-1210.1988"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.60.2.589-598.1986"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81775-4"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051173"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.24.5211"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1202-800"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2007.00986.x"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1719"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90227-4"},{"key":"e_1_3_4_71_2","unstructured":"J. P. 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