| First Author | Wong FS | Year | 2005 |
| Journal | Diabetes | Volume | 54 |
| Issue | 7 | Pages | 2032-40 |
| PubMed ID | 15983204 | Mgi Jnum | J:109830 |
| Mgi Id | MGI:3630006 | Doi | 10.2337/diabetes.54.7.2032 |
| Citation | Wong FS, et al. (2005) The influence of the major histocompatibility complex on development of autoimmune diabetes in RIP-B7.1 mice. Diabetes 54(7):2032-40 |
| abstractText | The most important genetic susceptibility factor for type 1 diabetes is encoded in the major histocompatibility complex (MHC). The nonobese diabetic (NOD) mouse, which develops spontaneous diabetes, expresses H-2g7 comprising the MHC class I molecules Kd and Db and the MHC class II molecule I-Ag7. However, neither B6.H-2g7 mice, in which H-2g7 is expressed on the C57BL/6 genetic background, nor the nonobese resistant (NOR) mouse, in which H-2g7 is expressed on a genetic background that is 88% similar to NOD mice, develop diabetes. Immune tolerance can be broken in these diabetes-resistant mice expressing H-2g7 if the costimulatory molecule B7.1 is present on the islet beta cells. This does not occur if only single MHC class I components of the H-2g7 haplotype are present, such as Kd in BALB/c mice or Db in C57BL/6 mice, both of which develop only a low level of diabetes when B7.1 is expressed. The presence of I-Ag7 leads to the development of an autoimmune T-cell repertoire, and local costimulation of CD8 T-cells precipitates aggressive diabetes. This implies that a major role of the MHC class II molecules in diabetes is the development of an autoreactive T-cell repertoire. |
