Lipid rafts and T cell receptor signaling: A critical re-evolution

Paola Pizzo, Emanuele Giurisato, Maristella Tassi, Angelo Benedetti, Tullio Possan, Antonella Viola

Research output: Contribution to journalArticlepeer-review

Abstract

The current model suggesting that raft integrity is required for T cell activation is mostly (but not exclusively) based on the use of drugs, such as methyl-β-cyclodextrin (MβCD), that disorganize rafts and inhibit T cell receptor (TCR)-induced Ca2+ influx. Here we show that conditions that disrupt lipid raft integrity do not inhibit TCR triggering in Jurkat cells and normal T lymphocytes. Indeed, we found that the reported inhibition of TCR-induced Ca2+ influx by MβCD treatment is mainly due to (a) nonspecific depletion of intracellular Ca2+ stores and (b) plasma membrane depolarization of T cells. When these side-effects are taken into account, raft disorganization does not alter TCR-dependent Ca2+ signaling. In line with these results, also TCR-induced tyrosine phosphorylation is not inhibited by dispersion of lipid rafts. By contrast, in the same conditions, Ca2+ signaling via the glycosylphosphatidylinositol (GPI)-anchored protein CD59 is totally abolished. These results indicate that, while signaling through GPI-anchored proteins requires lipid raft integrity, CD3-dependent TCR activation occurs independently of cholesterol extraction.

Original languageEnglish
Pages (from-to)3082-3091
Number of pages10
JournalEuropean Journal of Immunology
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 2002

Keywords

  • Ca signaling
  • Raft
  • T cell activation
  • TCR triggering

ASJC Scopus subject areas

  • Immunology

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