Nature Immunology
3, 483 - 488 (2002)
Published online: 1 April 2002; | doi:10.1038/ni779
A critical role for the cytoplasmic tail of pT in T lymphocyte developmentIannis Aifantis1, 4, Christine Borowski1, 4, Fotini Gounari1, H. Daniel Lacorazza2, Janko Nikolich-Zugich3
& Harald von Boehmer11
Department of Pathology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA. 2
Laboratory of Molecular Aspects of Hematopoiesis, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. 3
Vaccine and Gene Therapy Institute, Oregon Health and Science University West Campus, Beaverton, OR 97006, USA. 4
These authors contributed equally to this work.
Correspondence should be addressed to Harald von Boehmer Harald_von_Boehmer@dfci.harvard.eduSignals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the   T cell lineage. In contrast to the   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-TCR chain (pT). 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 pT mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pT cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pT juxtamembrane cysteine appeared to be dispensable for pre-TCR function.
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