The role of antigen presentation as a possible mechanism underlying major histocompatibility complex (MHC) association of autoimmune disease has been studied in non-obese diabetic (NOD) mice. By screening for inhibition of antigen presentation to NOD T cell hybridoma, we have selected a synthetic peptide, yTYTVHAAHAYTYt (small letters denote D amino acids), that efficiently blocks antigen presentation by the NOD class II MHC molecule A alpha g7A beta g7 (Ag7) in vitro. The inhibition is MHC selective, in that it does not affect antigen presentation by the E(d) and E(k) molecules, and has only a marginal effect on presentation by the A(d) molecule. This peptide also inhibits the priming for Ag7-restricted T cell responses in vivo, and prevents the spontaneous development of diabetes in female NOD mice, when administered chronically from 3 wk of age on. Chronic treatment with a control peptide, KMKMVHAAHAKMKM, that fails to bind to Ag7 has no effect on the disease. These data indicate that antigen presentation by the Ag7 molecule plays a pivotal role in the induction of autoimmune diabetes. Furthermore, the results demonstrate that interference with antigen presentation by a class II molecule can prevent the onset of spontaneous autoimmune disease associated with the same molecule.
Prevention of autoimmune diabetes in non-obese diabetic mice by treatment with a class II major histocompatibility complex-blocking peptide.
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U Hurtenbach, E Lier, L Adorini, Z A Nagy; Prevention of autoimmune diabetes in non-obese diabetic mice by treatment with a class II major histocompatibility complex-blocking peptide.. J Exp Med 1 May 1993; 177 (5): 1499–1504. doi: https://doi.org/10.1084/jem.177.5.1499
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