Antibody-mediated targeting of a hybrid-insulin-peptide towards neonatal thymic Langerin+ cells enhances T cell central tolerance and delays autoimmune diabetes

• DOI: 10.2337/figshare.19799728
• Publication Date: 2022-05-27T14:53:35Z
• Authors: Yong Lin; Jelena Perovanovic; Yuelin Kong; Botond Z. Igyarto; Sandra Zurawski; Dean Tantin; Gerard Zurawski; Maria Bettini; Matthew L. Bettini
• Keywords: Langerin; Central tolerance; NOD mice

<p> </p> <p>Thymic presentation of self-antigens is critical for establishing a functional yet self-tolerant T cell population. Hybrid peptides formed through transpeptidation within pancreatic beta lysosomes have been proposed as new class autoantigens in Type 1 Diabetes (T1D). While the production hybrid thymus has not explored, due to nature their generation, it thought be highly unlikely. Therefore, peptide-reactive thymocytes may preferentially escape thymic selection and contribute significantly T1D progression. Using an antibody-peptide conjugation system, we targeted 2.5HIP peptide towards resident Langerin+ dendritic cells enhance during early neonatal period. Our results indicated that anti-Langerin-2.5HIP delivery can central tolerance toward cognate NOD.BDC2.5 mice. Strikingly, single dose treatment with period delayed diabetes onset NOD mice, indicating potential antibody-mediated autoimmune neo-antigens stages life therapeutic option prevention diseases.</p>