Browsing by Subject "MHC II/Insulin complex"

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    Corrigendum: Regulatory T cells targeting a pathogenic MHC class II: insulin peptide epitope postpone spontaneous autoimmune diabetes
    (Frontiers Media, 2024-03-07) Obarorakpor, Nyerhovwo; Patel, Deep; Boyarov, Reni; Amarsaikhan, Nansalmaa; Cepeda, Joseph Ray; Eastes, Doreen; Robertson, Sylvia; Johnson, Travis; Yang, Kai; Tang, Qizhi; Zhang, Li; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    In the published article, there was an error in the Funding statement. Grant “JDRF 2-SRA-2018-648-S-B” grant was missing in the statement. The correct Funding statement appears below. Funding This study was supported by grants from NIH R03AI139811-01A1, DoD W81XWH2210087, JDRF 2-SRA-2018-648-S-B, and a Pilot and Feasibility Award from the CDMD NIH/NIDDK Grant Number P30 DK097512 (to LZ). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.
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    Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes
    (Frontiers Media, 2023-08-01) Obarorakpor, Nyerhovwo; Patel, Deep; Boyarov, Reni; Amarsaikhan, Nansalmaa; Cepeda, Joseph Ray; Eastes, Doreen; Robertson, Sylvia; Johnson, Travis; Yang, Kai; Tang, Qizhi; Zhang, Li; Biostatistics and Health Data Science, School of Medicine
    Introduction: In spontaneous type 1 diabetes (T1D) non-obese diabetic (NOD) mice, the insulin B chain peptide 9-23 (B:9-23) can bind to the MHC class II molecule (IAg7) in register 3 (R3), creating a bimolecular IAg7/InsulinB:9-23 register 3 conformational epitope (InsB:R3). Previously, we showed that the InsB:R3-specific chimeric antigen receptor (CAR), constructed using an InsB:R3-monoclonal antibody, could guide CAR-expressing CD8 T cells to migrate to the islets and pancreatic lymph nodes. Regulatory T cells (Tregs) specific for an islet antigen can broadly suppress various pathogenic immune cells in the islets and effectively halt the progression of islet destruction. Therefore, we hypothesized that InsB:R3 specific Tregs would suppress autoimmune reactivity in islets and efficiently protect against T1D. Methods: To test our hypothesis, we produced InsB:R3-Tregs and tested their disease-protective effects in spontaneous T1D NOD.CD28-/- mice. Results: InsB:R3-CAR expressing Tregs secrete IL-10 dominated cytokines upon engagement with InsB:R3 antigens. A single infusion of InsB:R3 Tregs delayed the onset of T1D in 95% of treated mice, with 35% maintaining euglycemia for two healthy lifespans, readily home to the relevant target whereas control Tregs did not. Our data demonstrate that Tregs specific for MHC class II: Insulin peptide epitope (MHCII/Insulin) protect mice against T1D more efficiently than polyclonal Tregs lacking islet antigen specificity, suggesting that the MHC II/insulin-specific Treg approach is a promising immune therapy for safely preventing T1D.