Lipid rafts mediate association of LFA-1 and CD3 and formation of the immunological synapse of CTL.
Lipid rafts accumulate in the immunological synapse formed by an organized assembly of the TCR/CD3, LFA-1, and signaling molecules. However, the precise role of lipid rafts in the formation of the immunological synapse is unclear. In this study, we show that LFA-1 on CTL is constitutively active and mediates Ag-independent binding of CTL to target cells expressing its ligands. LFA-1 and CD3 on CTL, but not resting T cells, colocalize in lipid rafts. Binding of LFA-1 on CTL to targets initiates the formation of the immunological synapse, which is formed by LFA-1, CD3, and ganglioside GM1 distributed in the periphery of the cell contact site and cholesterol is more widely distributed. The formation of this synapse is Ag independent, but the recognition of Ag by the TCR induces accumulation of tyrosine phosphorylated proteins in the synapse as well as redistribution of the microtubule organization center toward the cell contact site. Our results suggest that LFA-1 recruits lipid rafts and the TCR/CD3 to the synapse, and facilitates efficient and rapid activation of CTL.
Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada.
Muhammad Reza
MR
Marwali
Matthew A
MA
MacLeod
David N
DN
Muzia
Fumio
F
Takei
D000818:Animals; D000941:Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D003505:Cyclodextrins / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D022101:Microtubule-Organizing Center / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D047392:beta-Cyclodextrins
D000941:Antigens; D017252:CD3 Complex; D003505:Cyclodextrins; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin