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CUTTING EDGE |
Department of Pathology, Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110
The diabetes-susceptible class II MHC genes (in human and mouse) share unique nonaspartic acid residues at position 57 of the class II ß-chain. Transgenic expression of a mutant I-Ag7, substituting histidine and serine at position 56 and 57 of ß-chain with proline and aspartic acid (I-Ag7PD), respectively, inhibits diabetes development in the nonobese diabetic mouse model. Here, we demonstrate that immature thymocytes expressing a diabetogenic islet Ag-specific transgenic TCR are positively selected by I-Ag7PD class II MHC to give rise to mature CD4+ T cells. However, splenic APCs expressing the same I-Ag7PD fail to present pancreatic islet Ag to mature T cells bearing this diabetogenic TCR. These results indicate that nonaspartic acid residues at position 57 of class II MHC ß-chain is important for diabetogenic CD4+ T cell activation in the periphery but is not essential for the formation of a diabetogenic T cell repertoire in the thymus.
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