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Rockefeller University Press, Journal of Experimental Medicine, 10(210), p. 1911-1918, 2013

DOI: 10.1084/jem.20130876

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Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes

Journal article published in 2013 by Taras Kreslavsky, Hye-Jung Kim, Sergei B. Koralov ORCID, Dvora Ghitza, Thorsten Buch, Harvey Cantor, Klaus Rajewsky, Harald von Boehmer
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Antigen receptor editing—a process of secondary rearrangements of antigen receptor genes in autoreactive lymphocytes—is a well-established tolerance mechanism in B cells, whereas its role in T cells remains controversial. Here, we investigated this issue using a novel Tcra knock-in locus, which ensured appropriate timing of TCRα expression and allowed secondary rearrangements. Under these conditions the only response to self-antigen that could be unambiguously identified was negative selection of CD4/CD8 double positive thymocytes. No evidence could be obtained for antigen-induced TCR editing, whereas replacement of the transgenic TCRα chain by ongoing gene rearrangement occurred in some cells irrespective of the presence or absence of self-antigen.