Retro-inverso D-peptides as a novel targeted immunotherapy for Type 1 diabetes.
Retro-inverso D-peptides as a novel targeted immunotherapy for Type 1 diabetes.
J Autoimmun. 2020 Sep 17;:102543
Authors: Lombardi A, Concepcion E, Hou H, Arib H, Mezei M, Osman R, Tomer Y
Abstract
Over the past four decades, the number of people with Type 1 Diabetes (T1D) has increased by 4% per year, making it an important public health challenge. Currently, no curative therapy exists for T1D and the only available treatment is insulin replacement. HLA-DQ8 has been shown to present antigenic islet peptides driving the activation of CD4+ T-cells in T1D patients. Specifically, the insulin peptide InsB:9-23 activates self-reactive CD4+ T-cells, causing pancreatic beta cell destruction. The aim of the current study was to identify retro-inverso-d-amino acid based peptides (RI-D-peptides) that can suppress T-cell activation by blocking the presentation of InsB:9-23 peptide within HLA-DQ8 pocket. We identified a RI-D-peptide (RI-EXT) that inhibited InsB:9-23 binding to recombinant HLA-DQ8 molecule, as well as its binding to DQ8 expressed on human B-cells. RI-EXT prevented T-cell activation in a cellular antigen presentation assay containing human DQ8 cells loaded with InsB:9-23 peptide and murine T-cells expressing a human T-cell receptor specific for the InsB:9-23-DQ8 complex. Moreover, RI-EXT blocked T-cell activation by InsB:9-23 in a humanized DQ8 mice both ex vivo and in vivo, as shown by decreased production of IL-2 and IFN-γ and ...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Lombardi A, Concepcion E, Hou H, Arib H, Mezei M, Osman R, Tomer Y Tags: J Autoimmun Source Type: research
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