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T-cell development

Understanding why T-cell receptors remain single

Nature Reviews Immunology volume 5, page 95 (2005)Cite this article

TCR-β allelic exclusion is regulated at two stages of thymocyte development: at the double negative (DN) stage, when the TCR-β alleles must rearrange asynchronously; and at the double positive (DP) stage — which is reached only after a maturation signal from the pre-TCR indicates successful TCR-β gene rearrangement — when further TCR-β gene rearrangement must be prevented. In this study, Jackson et al. set out to investigate the proposed role of Vβ gene-segment accessibility in the inhibition of Tcr-β gene rearrangement after transition to the DP stage. They generated knock-in mice expressing a modified Tcr-β allele in which the Tcr-α enhancer (Eα) was positioned downstream of the Vβ12 gene segment. Consistent with their hypothesis that the introduced Eα (Eαi) would maintain the Vβ chromatin in an active configuration in DP thymocytes, DP thymocytes from knock-in mice showed increased Vβ germline transcription, histone modification and restriction-endonuclease accessibility compared with DP thymocytes from wild-type animals.

Vβ-to-DJβ rearrangement is downregulated in DP thymocytes from wild-type mice compared with rearrangement in DN thymocytes from the same animals. Surprisingly, despite the presence of Eαi increasing Vβ chromatin activation (and therefore accessibility) in DP thymocytes, Vβ-to-DJβ rearrangement in these cells was also downregulated compared with rearrangement in DN thymocytes.

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ORIGINAL RESEARCH PAPER

  1. Jackson, A., Kondilis, H. D., Khor, B., Sleckman, B. P. & Krangel, M. S. Regulation of T cell receptor β allelic exclusion at a level beyond accessibility. Nature Immunol. 6, 189–197 (2005).

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  1. Karen Honey
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Honey, K. Understanding why T-cell receptors remain single. Nat Rev Immunol 5, 95 (2005). https://doi.org/10.1038/nri1560

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  • DOI: https://doi.org/10.1038/nri1560

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