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

Nature Immunology
Iannis AifantisHarald von Boehmer

Abstract

Signals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the alphabeta T cell lineage. In contrast to the gammadelta 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-TCRalpha chain (pTalpha). 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 pTalpha mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pTalpha cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pTalpha juxtamembrane cysteine appeared to be dispensable for pre-TCR function.

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Citations

Jan 21, 2012·Nature Immunology·Gerald P Morris, Paul M Allen
Jan 24, 2007·Nature Immunology·Adrian C Hayday, Daniel J Pennington
Jul 7, 2005·Nature Reviews. Immunology·Harald von Boehmer
Nov 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·Philippe SmeltyJulien S Fellah
Oct 30, 2010·Proceedings of the National Academy of Sciences of the United States of America·Eri IshikawaSho Yamasaki
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Feb 25, 2005·The Journal of Experimental Medicine·Malay MandalIannis Aifantis
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Nov 5, 2008·The Journal of Experimental Medicine·Xiaoyu LiHarald von Boehmer
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Jun 10, 2021·Journal of Inflammation Research·Chunling ZhaoJianfeng Zhang

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