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A critical role for the cytoplasmic tail of pTα in T lymphocyte development

Nature Immunology volume 3, pages 483488 (2002) | Download Citation

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  • A Corrigendum to this article was published on 01 June 2002

Abstract

Signals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the αβ T cell lineage. In contrast to the γδ TCR, the pre-TCR localizes cell-autonomously to membrane rafts, where it appears to signal in a constitutive and ligand-independent manner. We addressed here the role played by structural features specific to the cytoplasmic domain of the pre-TCRα chain (pTα). More specifically, we examined a COOH-terminal proline-rich sequence that might play a role in signal transduction and a juxtamembrane cysteine residue that could be a target for palmitoylation, thus allowing spontaneous raft localization. Expression of pTα mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pTα cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pTα juxtamembrane cysteine appeared to be dispensable for pre-TCR function.

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Acknowledgements

Supported by the NIH (grants A147281 and A145846 to H. v. B.), a “Eugenia Spanopoulou” – Irvington Institute grant (to I. A.) and a National Science Foundation grant (to C. B.). We thank B. Reizis for LR2 cell line and R. Mulligan for the MMLV-based retroviral vector; M. Prakriya and L. Scorrano for their advice and help with the Ca2+ measurements; S. Hoeflinger for technical assistance; H. Levine and M. Cantley for cell sorting; and E. Smith for help with preparation of the manuscript.

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Author notes

    • Iannis Aifantis
    •  & Christine Borowski

    These authors contributed equally to this work.

Affiliations

  1. Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

    • Iannis Aifantis
    • , Christine Borowski
    • , Fotini Gounari
    •  & Harald von Boehmer
  2. Laboratory of Molecular Aspects of Hematopoiesis, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

    • H. Daniel Lacorazza
  3. Vaccine and Gene Therapy Institute, Oregon Health and Science University West Campus, Beaverton, OR 97006, USA.

    • Janko Nikolich-Zugich

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The authors declare no competing financial interests.

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Correspondence to Harald von Boehmer.

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DOI

https://doi.org/10.1038/ni779