| First Author | Levisetti MG | Year | 2008 |
| Journal | Diabetes | Volume | 57 |
| Issue | 7 | Pages | 1852-60 |
| PubMed ID | 18398138 | Mgi Jnum | J:138230 |
| Mgi Id | MGI:3804587 | Doi | 10.2337/db08-0068 |
| Citation | Levisetti MG, et al. (2008) Weak proinsulin peptide-major histocompatibility complexes are targeted in autoimmune diabetes in mice. Diabetes 57(7):1852-60 |
| abstractText | OBJECTIVE: Weak major histocompatibility complex (MHC) binding of self-peptides has been proposed as a mechanism that may contribute to autoimmunity by allowing for escape of autoreactive T-cells from the thymus. We examined the relationship between the MHC-binding characteristics of a beta-cell antigen epitope and T-cell autoreactivity in a model of autoimmune diabetes. RESEARCH DESIGN AND METHODS: The binding of a proinsulin epitope, proinsulin-1(47-64) (PI-1[47-64]), to the MHC class II molecules I-A(g7) and I-A(k) was measured using purified class II molecules. T-cell reactivity to the proinsulin epitope was examined in I-A(g7+) and I-A(k+) mice. RESULTS: C-peptide epitopes bound very weakly to I-A(g7) molecules. However, C-peptide-reactive T-cells were induced after immunization in I-A(g7)-bearing mice (NOD and B6.g7) but not in I-A(k)-bearing mice (B10.BR and NOD.h4). T-cells reactive with the PI-1(47-64) peptide were found spontaneously in the peripancreatic lymph nodes of pre-diabetic NOD mice. These T-cells were activated by freshly isolated beta-cells in the presence of antigen-presenting cells and caused diabetes when transferred into NOD.scid mice. CONCLUSIONS: These data demonstrate an inverse relationship between self-peptide-MHC binding and T-cell autoreactivity for the PI-1(47-64) epitope in autoimmune diabetes. |
