Recombinase-deficient T cell development by selective accumulation of CD3 into lipid rafts

Denise Ferrera, Maddalena Panigada, Simona Porcellini, Fabio Grassi

Research output: Contribution to journalArticlepeer-review

Abstract

The pre-T cell receptor (pre-TCR) promotes the development of thymocytes with productive rearrangement at the TCR β chain locus by signaling in a ligand-independent fashion. The TCR β chain associates with the invariant pre-Tα (pTα) chain, which bears specific charged residues in the extracellular portion mediating pre-TCR self-oligomerization. In recombinase-deficient thymocytes, calnexin (CNX) associated with CD3 chains is inefficiently retained in the endoplasmic reticulum (ER) and weakly expressed in the plasma membrane. Deliberate cross-linking of CNX/CD3 complexes mimics pre-TCR signaling. Here, we show that, analogously to the pTα chain, surface CNX is palmitoylated and that CD3 prominently accumulated in lipid rafts upon cross-linking. Mutant CNX isoforms devoid of ER retention determined pre-TCR-like signaling and simulated β selection only when stably translocating CD3 to lipid rafts. Inclusion of the palmitoylated cytoplasmic tail from the pTα chain in recombinant CNX strikingly improved the pre-TCR-like signaling efficiency of CNX/CD3 in rafts. This study indicates that lipid rafts in the plasma membrane represent proficient microdomains for the initiation of pre-TCR signaling, and supports the view that β selection by oligomerized pre-TCR is implemented by the pTα cytoplasmic tail.

Original languageEnglish
Pages (from-to)1148-1156
Number of pages9
JournalEuropean Journal of Immunology
Volume38
Issue number4
DOIs
Publication statusPublished - Apr 2008

Keywords

  • Developmental immunology
  • Lipid rafts
  • Signal transduction
  • Thymopoiesis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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