TY - JOUR
T1 - Lipid rafts and T cell receptor signaling
T2 - A critical re-evolution
AU - Pizzo, Paola
AU - Giurisato, Emanuele
AU - Tassi, Maristella
AU - Benedetti, Angelo
AU - Possan, Tullio
AU - Viola, Antonella
PY - 2002/11
Y1 - 2002/11
N2 - 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.
AB - 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.
KW - Ca signaling
KW - Raft
KW - T cell activation
KW - TCR triggering
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U2 - 10.1002/1521-4141(200211)32:11<3082::AID-IMMU3082>3.0.CO;2-2
DO - 10.1002/1521-4141(200211)32:11<3082::AID-IMMU3082>3.0.CO;2-2
M3 - Article
C2 - 12385028
AN - SCOPUS:0036857767
VL - 32
SP - 3082
EP - 3091
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 11
ER -