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Regulation of the TCRα repertoire by the survival window of CD4+CD8+ thymocytes

Nature Immunology volume 3, pages 469476 (2002) | Download Citation

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Abstract

T cell receptor (TCR) α alleles undergo primary and secondary rearrangement in double-positive (DP) thymocytes. By analyzing TCRα rearrangement in orphan nuclear receptor RORγ-deficient mice, in which the DP lifespan is shorter, and in Bcl-xL–transgenic mice, in which the DP lifespan is extended, we show that the progression of secondary Vα to Jα rearrangements is controlled by DP thymocyte survival. In addition, because Bcl-xL induces a bias towards 3′ Jα usage in peripheral T cells, we conclude that the programmed cell death of DP thymocytes is not simply a consequence of failed positive selection. Rather, it limits the progression of rearrangement along the Jα locus and the opportunities for positive selection, thereby regulating the TCRα repertoire.

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Acknowledgements

We thank H. Yin for help with Southern blot analysis; M. Cook in the Flow Cytometry Facility of DUMC for help on cell sorting; and W. O'Brien and M. J. Sunshine for help with the mouse breeding and typing. Supported by grant RSG-0125201 from the American Cancer Society (to Y.-W. H.) and NIH grants GM41052 (to M. S. K.) and AI33856 (to D. R. L.).

Author information

Author notes

    • Zuoming Sun

    Present address: Department of Microbiology and Immunology (M/C 790), University of Illinois, 835 S. Wolcott, Chicago, IL 60612, USA.

Affiliations

  1. Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

    • Jian Guo
    • , Abbas Hawwari
    • , Hong Li
    • , Michael S. Krangel
    •  & You-Wen He
  2. Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA.

    • Zuoming Sun
    • , Sanjeev K. Mahanta
    •  & Dan R. Littman
  3. HHMI, New York University School of Medicine, New York, NY 10016, USA.

    • Dan R. Littman

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The authors declare no competing financial interests.

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Correspondence to You-Wen He.

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https://doi.org/10.1038/ni791