Kreslavsky, TarasKim, Hye-JungKoralov, Sergei B.Ghitza, DvoraBuch, ThorstenCantor, HarveyRajewsky, Klausvon Boehmer, Harald2014-04-112013Kreslavsky, Taras, Hye-Jung Kim, Sergei B. Koralov, Dvora Ghitza, Thorsten Buch, Harvey Cantor, Klaus Rajewsky, and Harald von Boehmer. 2013. “Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes.” The Journal of Experimental Medicine 210 (10): 1911-1918. doi:10.1084/jem.20130876. http://dx.doi.org/10.1084/jem.20130876.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:12064485Antigen 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.en-USJournal Article2014-04-1110.1084/jem.20130876