CD59 functions as a signal-transducing molecule for human T cell activation.
The CD59 Ag is a 20-kDa protein that is widely expressed on most leukocytes and RBC, is coupled to the membrane by a phosphatidylinositol-glycan anchoring structure, plays a role in cell interaction between monocytes and T cells, and also functions as an inhibitor of cytolysis by the terminal C components C5b-9. Because this molecule is structurally related to the murine Ly-6 family of Ag, we have investigated whether anti-CD59 mAb might be capable of activating human T lymphocytes in a manner similar to that described for antibodies to the murine Ly-6 Ag. In the presence of the appropriate co-stimulators, mAb to one of the two epitopes on CD59 were capable of inducing both a rise in intracytoplasmic free Ca2+, inositol phosphate production, IL-2 production, and T cell proliferation. Anti-CD59-induced inositol phosphate turnover and IL-2 production were dependent on co-expression of the CD3/TCR complex. CD59-loss mutants of the Jurkat cell line were completely responsive to stimulation by anti-CD3 thereby demonstrating that CD59 does not play a role as a signal transducer downstream from the TCR. Taken together, these results demonstrate that the CD59 Ag can play multiple distinct roles in the regulation of the immune response.
Korty
P E
PE
Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Brando
C
C
Shevach
E M
EM
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology; D017252:CD3 Complex; D018957:CD59 Antigens; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D018957:CD59 Antigens; D007295:Inositol Phosphates; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D002118:Calcium