Working with nonobese diabetic (NOD) mice, the investigators unveiled the mechanisms through which MHC class II molecules promote resistance to type 1diabetes. They genetically engineered NOD mice to either express diabetes-promoting or -suppressing MHC class II molecules and compared the effects of these molecules on the development and function of diabetes-causing white blood cells.
These studies revealed that dendritic cells, a white blood cell type which is responsible for orchestrating most immune responses, can “trick” disease-causing (autoreactive) white blood cells into becoming disease-suppressing ones, by “presenting” the protective MHC molecules on their surface. The authors propose that this mechanism may underlie the association of MHC class II genetic variation with other autoimmune conditions.
Reference: Tsai S, Serra P, Clemente-Casares X, Yamanouchi J, Thiessen S, Slattery RM, Elliott JF, Santamaria P. Antidiabetogenic MHC class II promotes the differentiation of MHC-promiscuous autoreactive T cells into FOXP3+ regulatory T cells. Proc Natl Acad Sci U S A. 2013 Feb 26; 110(9): 3471-6. doi: 10.1073/pnas.1211391110. Epub 2013 Feb 11.