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J. Exp. Med.,
Volume 189, Number 1, January 4, 1999 13-24
By

From the * Howard Hughes Medical Institute, and the Department of Microbiology and Immunology,
Stanford University, Stanford, California 94305; the To investigate the influence of endogenous peptides on the developmental processes that occur
during thymocyte selection, we have used monoclonal antibodies that preferentially recognize the major histocompatibility complex (MHC) molecule I-Ek when it is bound to the moth cytochrome c peptide (88-103). One of these antibodies (G35) specifically blocks the positive selection of transgenic thymocytes expressing a T cell receptor that is reactive to this peptide-
MHC complex. Furthermore, G35 does not block the differentiation of transgenic T cells
bearing receptors for a different I-Ek-peptide complex. This antibody recognizes a subset of
endogenous I-Ek-peptide complexes found on a significant fraction of thymic antigen-presenting cells, including cortical and medullary epithelial cells. The sensitivity of G35 to minor alterations in peptide sequence suggests that the thymic peptide-MHC complexes that mediate the
positive selection of a particular class II MHC-restricted thymocyte are structurally related to
the complexes that can activate it in the periphery.
Department of Biological Structure and
Department of Immunology, School of Medicine, University of Washington, Seattle, Washington
98195; and the § Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe
Hospital, Headington, OX3 9DU, United Kingdom
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