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

作者:Kreslavsky Taras; Kim Hye Jung; Koralov Sergei B; Ghitza Dvora; Buch Thorsten; Cantor Harvey; Rajewsky Klaus; von Boehmer Harald*
来源:Journal of Experimental Medicine, 2013, 210(10): 1911-1918.
DOI:10.1084/jem.20130876

摘要

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 TCR alpha 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 TCR alpha chain by ongoing gene rearrangement occurred in some cells irrespective of the presence or absence of self-antigen.