title: Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes.
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.
authors: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute; and 2 Program in Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115.
authors: Taras
authors: T
authors: Kreslavsky
authors: Hye-Jung
authors: HJ
authors: Kim
authors: Sergei B
authors: SB
authors: Koralov
authors: Dvora
authors: D
authors: Ghitza
authors: Thorsten
authors: T
authors: Buch
authors: Harvey
authors: H
authors: Cantor
authors: Klaus
authors: K
authors: Rajewsky
authors: Harald
authors: H
authors: von Boehmer
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D060966:Clonal Selection, Antigen-Mediated; D005260:Female; D023061:Gene Order; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D018390:Gene Targeting; D056426:Genetic Loci; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta
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