Abstract
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.
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McGargill, M., Derbinski, J. & Hogquist, K. Receptor editing in developing T cells. Nat Immunol 1, 336–341 (2000). https://doi.org/10.1038/79790
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DOI: https://doi.org/10.1038/79790
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