Transgenic mice expressing a T cell receptor heterodimer specific for a fragment of pigeon cytochrome c plus an MHC class II molecule (I-Ek) have been made. We find that H-2kαβ transgenic mice have an overall increase in the number of T cells and express a 10-fold higher fraction of cytochrome c-reactive cells than H-2bmice. Surface staining of thymocytes indicates that in H-2bmice, T cell development is arrested at an intermediate stage of differentiation (CD4+8+, CD3lo). Analyses of mice carrying these T cell receptor genes and MHC class II I-Eαconstructs indicate that this developmental block can be reversed in H-2bmice by I-E expression on cortical epithelial cells of the thymus. These data suggest that a direct T cell receptor-MHC interaction occurs in the thymus in the absence of nominal antigen and results in the enhanced export of T cells, consistent with the concept of "positive selection.". © 1989.
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