Recently, peptide library technology identified mimotopes that proved reactive with the highly diabetogenic BDC2.5 T cells. Herein, we propose to express these mimotopes on immunoglobulins (Ig) to increase tolerogenic functions and test for prevention of diabetes in young mice as well as reversal of the disease in insulitis-positive and prediabetic animals. ? ? Because the Ig-mimotopes will likely internalize into antigen presenting cells (APCs) mainly via Fc receptors (FcRs), their processing will take place in endosomes granting access to newly synthesized major histocompatibility complex (MHC) molecules and enhancing loading of the mimotopes onto MHC molecules. The end results should be magnified presentation to T cells. ? ? Since the chimeras will be injected into animals without adjuvant costimulation should be lacking and the enhanced presentation is expected to drive tolerance rather than immunity. Moreover, if the chimeras are aggregated, cross-linking of FcRs could occur, leading to IL-10 production by the APCs. IL-10 should amplify the tolerogenic function of the chimeras either by bystander suppression of pathogenic T cells and/or by facilitating the development of regulatory T cells. Our hypothesis postulates that presentation of the mimotopes on Igs could target highly diabetogenic T cells for effective down-regulation and reverse the ongoing pathological processes of T1D. ? ? ?
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