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Receptor editing in developing T cells

Nature Immunology volume 1, pages 336–341 (2000)Cite this article

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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Figure 1: Expression of the transgene encoding K14-OVAp in thymic cortical epithelial cells.
Figure 2: Activation, but not deletion, of DP thymocytes.
Figure 3: TCRlo DP thymocytes are not selectively expanded.
Figure 4: Re-expression of the transgenic TCR.
Figure 5: Mixed bone marrow chimeras.
Figure 6: Cortical expression of antigen increased RAG mRNA and endogenous rearrangements at the α locus in DP thymocytes.
Figure 7: Cortical expression of antigen increases the number of cells expressing endogenous α chains.
Figure 8: Activation of CD8 T cells in the periphery.

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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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  1. Department of Laboratory Medicine and Pathology, the Center for Immunology University of Minnesota, Minneapolis , 55455, MN, USA

    Maureen A. McGargill, Jens M. Derbinski & Kristin A. Hogquist

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  1. Maureen A. McGargill
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  3. Kristin A. Hogquist
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Correspondence to Kristin A. Hogquist.

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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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