Tolerance to class II MHC in transgenic mice

Transgenic mice offer new possibilities in experimental techniques for understanding the familiar questions of T cell development and the selection of the T cell repertoire. As a powerful method to manipulate gene expression in the whole animal, precisely defined in vivo models can be developed. In our own studies, we have used transgenic mice with targeted expression of I-E and new monoclonal antibodies defining T cell receptors specific for class II I-E molecules. In the thymus, our results suggest that thymic epithelium has significant tolerance inducing capability, but the mechanism may be different from the clonal deletion induced by bone marrow derived cells. In the periphery, our results suggest that tolerance to tissue restricted antigens is not induced by clonal deletion. Instead, clonal paralysis may be an important mechanism for both inducing and maintaining peripheral tolerance.