An antibody present in normal human serum inhibits the binding of cytokines to their receptors in an in vitro system.
The presence of active transforming growth factor-beta (TGF-beta) in serum has not been widely accepted. In particular, although at least five studies have concluded that active TGF-beta is present in normal human plasma and serum, assays that use the extracellular domain of the TGF-beta type II receptor as a capture agent have given contradictory results. We show that there is an antagonist present in normal human serum which inhibits the binding of active TGF-beta to the extracellular domain of the TGF-beta type II receptor when it is coated on the well of an ELISA plate. This antagonist activity is due to a pool of immunoglobulins of the G2, D and M classes. Moreover, we show that this same pool of immunoglobulins also recognizes the extracellular domain of the platelet-derived growth factor alpha-receptor, insulin-like growth factor-1 receptor and interleukin-3 receptor, by serial transfer of serum over the different receptors. In addition, the same immunoglobulin pool inhibits the binding of platelet-derived growth factor-AA to its receptor, in an analogous way to the inhibition of binding of TGF-beta to its type II receptor. Circumstantial evidence suggests that the pool of immunoglobulins is recognizing a carbohydrate residue that is attached to the protein when it is synthesized by the mouse myeloma cell line, NSO, in which it is made. If the cytokine receptors are similarly glycosylated in vivo, then the presence of these antibodies in normal human serum may modulate physiological cytokine signalling.
Mosedale
D E
DE
Department of Medicine, Box 157, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, U.K. dem@mole.bio.cam.ac.uk
Grainger
D J
DJ
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000906:Antibodies; D007136:Immunoglobulins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II