A central tenet of T cell development postulates that if a developing thymocyte encounters self-antigen, it is induced to die via apoptosis, thereby protecting the organism from autoreactive T cells. We created transgenic mice that expressed a peptide antigen in the cortical epithelial cells of the thymus. This did not, however, result in deletion of specific T cells. Instead, antigen presentation by epithelial cells caused T cell receptor (TCR) internalization and increased gene rearrangement at the endogenous TCRα locus, or receptor editing. This editing mechanism in immature T cells parallels that which occurs in immature B cells, and has important implications for understanding positive and negative selection signaling in the thymus, and the limits of self-tolerance.
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Acknowledgements We thank H. Stefanski, B. Koehn,A. Panoskaltsis-Mortari, J. Hermanson, S. Hermanson, N. Fujioka and D. Erlandson for technical assistance, and S. Jameson,T. Behrens, M. Jenkins and members of the Jameson and Hogquist labs for reading the manuscript. Supported by NIH grants AI35296-06,AI07313-12 and the Searle Scholars Fund.