Functional and physical association of a cell surface phospholipid and interleukin-2 receptor p55(alpha) subunits.
A phosphatidylcholine-like phospholipid expressed in the outer leaflet of the cell membrane shortly after mitogenic activation of T-cells is described, based on the binding of monoclonal antibody 90. 60.3. Expression of the 90.60.3 phospholipid antigen in T-cells is activation-dependent. Once expressed, the 90.60.3 phospholipid is in direct physical association with the interleukin-2 (IL-2) binding domain of IL-2 receptor alpha subunits, but does not affect IL-2 binding. The association is specific, because the 90.60.3 phospholipid is not found in association with other domains of IL-2 receptor alpha subunits, or near IL-2 receptor beta or gamma subunits. Culturing cytokine-dependent cell lines in the presence of monoclonal antibody 90.60.3 potentiates IL-2-dependent cell survival and proliferation in a dose-dependent manner. In contrast, IL-4-dependent responses are not potentiated. Taken together, the data suggest that specific plasma membrane phospholipids expressed in the outer leaflet after T-cell activation associate with the IL-2 binding domain of IL-2 receptor alpha subunits (and perhaps other cytokine receptors), and may play a role in regulating receptor mobility or signal transduction.
Saragovi
H U
HU
McGill University, Department of Pharmacology and Therapeutics, 3655 Drummond 1320; and McGill Cancer Center, Montreal, QC H3G1Y6, Canada. uri@pharma.mcgill.ca
Bhandoola
A
A
Moreau
J L
JL
Lavine
N
N
Gagnon
M
M
Lemercier
M M
MM
Théze
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens; D010743:Phospholipids / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D008934:Mitogens; D010743:Phospholipids; D015375:Receptors, Interleukin-2