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Through the engineering of an HLA-DR1 chimeric Ag receptor (CAR), we have produced CD8+ CAR T cells that target CD4+ T cells in an Ag-specific manner and tested their ability to inhibit the development of autoimmune arthritis in a mouse model. The DR1 CAR molecule was engineered to contain CD3\u03b6 activation and CD28 signaling domains and a covalently linked autoantigenic peptide from type II collagen (CII; DR1-CII) to provide specificity for targeting the autoimmune T cells. Stimulation of the DR1-CII CAR T cells by an anti-DR Ab induced cytokine production, indicating that the DR1-CAR functions as a chimeric molecule. In vitro CTL assays using cloned CD4+ T cells as target cells demonstrated that the DR1-CII CAR T cells efficiently recognize and kill CD4+ T cells that are specific for the CII autoantigen. The CTL function was highly specific, as no killing was observed using DR1-restricted CD4+ T cells that recognize other Ags. When B6.DR1 mice, in which autoimmune arthritis had been induced, were treated with the DR1-CII CAR T cells, the CII-specific autoimmune CD4+ T cell response was significantly decreased, autoantibody production was suppressed, and the incidence and severity of the autoimmune arthritis was diminished. These data demonstrate that HLA-DR CAR T cells have the potential to provide a highly specific therapeutic approach for the treatment of autoimmune disease.<\/jats:p>","DOI":"10.4049\/jimmunol.2100643","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T17:20:39Z","timestamp":1637774439000},"page":"16-26","source":"Crossref","is-referenced-by-count":51,"title":["CD8+ T Cells Expressing an HLA-DR1 Chimeric Antigen Receptor Target Autoimmune CD4+ T Cells in an Antigen-Specific Manner and Inhibit the Development of Autoimmune Arthritis"],"prefix":"10.1093","volume":"208","author":[{"given":"Karen B","family":"Whittington","sequence":"first","affiliation":[{"name":"Veterans Affairs Medical Center , Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Prislovsky","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center , Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6008-9989","authenticated-orcid":false,"given":"Jacob","family":"Beaty","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Albritton","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center , Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8004-282X","authenticated-orcid":false,"given":"Marko","family":"Radic","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center , Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6225-5867","authenticated-orcid":false,"given":"Edward F","family":"Rosloniec","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center , Memphis TN"},{"name":"Department of Medicine, University of Tennessee Health Science Center , Memphis TN"},{"name":"Department of Pathology, University of Tennessee Health Science Center , Memphis TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"2025021008474955000_r1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.autrev.2012.02.001","article-title":"Updated assessment of the prevalence, spectrum and case definition of autoimmune disease","volume":"11","author":"Hayter","year":"2012","journal-title":"Autoimmun. 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