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

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Item Type:Article
Title:Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes
Creators Name:Kreslavsky, T., Kim, H.J., Koralov, S.B., Ghitza, D., Buch, T., Cantor, H., Rajewsky, K. and von Boehmer, H.
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.
Keywords:alpha-beta T-Cell Antigen Receptors, alpha-Chain T-Cell Antigen Receptor Gene Rearrangement, Antigen-Mediated Clonal Selection, Autoantigens, Gene Order, Gene Targeting, Genetic Loci, Phenotype, Transgenic Mice, Thymocytes, Animals, Mice
Source:Journal of Experimental Medicine
ISSN:0022-1007
Publisher:Rockefeller University Press
Volume:210
Number:10
Page Range:1911-1918
Date:23 September 2013
Official Publication:https://doi.org/10.1084/jem.20130876
PubMed:View item in PubMed

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