Physiological T cell activation starts and propagates in lipid rafts.
Lipid rafts are plasma membrane compartments enriched in key signaling molecules. We have previously shown that in T lymphocytes anti-CD3 stimulation is insensitive to cholesterol extraction by methyl-beta-cyclodextrin (MbetaCD), suggesting that anti-CD3 induced signal transduction is independent of raft integrity. Here we show that, in contrast to T cell stimulation by anti-CD3 antibodies, T cell activation by a physiological ligand is mediated by signaling events taking place in lipid raft. Indeed, cholesterol depletion by MbetaCD resulted in reduced T cell activation in response to Epstein Barr Virus (EBV)-transformed B cells pulsed with a bacterial superantigen. Moreover, T cell stimulation by pulsed EBV-B cells, but not by anti-CD3 antibodies, induced recruitment of active Lck in detergent-resistant membranes, where the signal transduction is organized and amplified.
Pizzo
Paola
P
Department of Biomedical Sciences, University of Padova, via G Colombo 3, 35121 Padova, Italy.
Giurisato
Emanuele
E
Bigsten
Anna
A
Tassi
Maristella
M
Tavano
Regina
R
Shaw
Andrey
A
Viola
Antonella
A
D000906:Antibodies / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology*; D021962:Membrane Microdomains / Q000276:immunology / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D002784:Cholesterol; D002118:Calcium