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

SUBMITTER: Kreslavsky T

PROVIDER: S-EPMC3782038 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Kreslavsky Taras T Kim Hye-Jung HJ Koralov Sergei B SB Ghitza Dvora D Buch Thorsten T Cantor Harvey H Rajewsky Klaus K von Boehmer Harald H

The Journal of experimental medicine 20130826 10

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 o ...[more]

PMID: 23980099

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