Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes
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Item Type: | Article |
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Title: | Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes |
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Creators Name: | Kreslavsky, T. and Kim, H.J. and Koralov, S.B. and Ghitza, D. and Buch, T. and Cantor, H. and Rajewsky, K. and von Boehmer, H. |
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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. |
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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 |
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Source: | Journal of Experimental Medicine |
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ISSN: | 0022-1007 |
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Publisher: | Rockefeller University Press |
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Volume: | 210 |
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Number: | 10 |
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Page Range: | 1911-1918 |
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Date: | 23 September 2013 |
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Official Publication: | https://doi.org/10.1084/jem.20130876 |
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PubMed: | View item in PubMed |
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