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Nat Immunol. 2016 Dec;17(12):1415-1423. doi: 10.1038/ni.3560. Epub 2016 Sep 26.

Timing and duration of MHC I positive selection signals are adjusted in the thymus to prevent lineage errors.

Author information

1
Experimental Immunology Branch, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA.
2
Laboratory of Mammalian Genes and Development, Eunice Kennedy Schriver National Institute of Child Health and Human Development, US National Institutes of Health, Bethesda, Maryland, USA.
3
Department of Immunology, Chiba University, Chiba, Japan.

Abstract

Major histocompatibility complex class I (MHC I) positive selection of CD8+ T cells in the thymus requires that T cell antigen receptor (TCR) signaling end in time for cytokines to induce Runx3d, the CD8-lineage transcription factor. We examined the time required for these events and found that the overall duration of positive selection was similar for all CD8+ thymocytes in mice, despite markedly different TCR signaling times. Notably, prolonged TCR signaling times were counter-balanced by accelerated Runx3d induction by cytokines and accelerated differentiation into CD8+ T cells. Consequently, lineage errors did not occur except when MHC I-TCR signaling was so prolonged that the CD4-lineage-specifying transcription factor ThPOK was expressed, preventing Runx3d induction. Thus, our results identify a compensatory signaling mechanism that prevents lineage-fate errors by dynamically modulating Runx3d induction rates during MHC I positive selection.

PMID:
27668801
DOI:
10.1038/ni.3560
[Indexed for MEDLINE]

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