Stimulation of the T-cell receptors CD3 and CD2 with OKT3 and OKT11 antibodies activates a common pertussis toxin-insensitive G-protein.
The association of G-proteins with the T-cell-specific receptor structures CD3 and CD2 was investigated. High-affinity GTPase activity in membrane preparations of the human leukemic T-cell line Jurkat could be induced by the monoclonal antibodies OKT3 (anti-CD3) and OKT11 (anti-CD2). When combining maximally active concentrations of OKT3 and OKT11, no additive effect was seen on GTPase activity. In mutant Jurkat cells lacking the CD3 complex but with an intact CD2 receptor, neither OKT3 nor OKT11 could stimulate GTPase activity. Activation of CD3 and CD2 by monoclonal antibodies also stimulated phospholipase C activity as measured by breakdown of membrane phosphoinositides in wild-type but not in mutant Jurkat cells. Neither GTPase nor phospholipase C activation was sensitive to pretreatment with doses of pertussis toxin (PTX) that caused ADP ribosylation of a sensitive G-protein. Our data show that the CD3 complex and the CD2 receptor may activate a common PTX-insensitive G-protein. The CD2 receptor appears to stimulate the G-protein by interacting with the CD3 complex. The data are compatible with, but do not prove, that this G-protein is involved in the activation of phospholipase C by the two receptors.
Kvanta
A
A
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Gerwins
P
P
van der Ploeg
I
I
Nordstedt
C
C
Jondal
M
M
Fredholm
B B
BB
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D018801:CD2 Antigens; D017252:CD3 Complex; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D006825:Hybridomas; D007295:Inositol Phosphates / Q000378:metabolism; D037342:Pertussis Toxin; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D004229:Dithiothreitol