MHC class II polymorphism and central tolerance in autoimmune diabetes.

摘要

Insulin-dependent diabetes mellitus is a complex disease characterized by the destruction of the pancreatic beta cells which produce insulin. A strong genetic link exist between autoimmunity and MHC class II polymorphism where different alleles infer either susceptibility or resistance from disease. The NOD mouse spontaneously develops IDDM and therefore provides an appropriate genetic background with which to study this disease. Previously it has been shown that T cells bearing an I-Ag7-restricted, beta cell reactive, highly diabetogenic T cell receptor (4.1-TCR) underwent negative selection when non-NOD MHC class II molecules were expressed in the 4.1-NOD background. Here it is shown that when 4.1-thymocytes interact with I-Ad, I-Ag7PD, or I-Eαk MHC class II molecules (expressed as transgenes) they undergo different levels of tolerance. Therefore, anti-diabetogenic MHC class II molecules may provide protection from disease by having a tolerogenic affect on highly pathogenic, 4.1-like CD4+ T cells.