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 rec eptor as a capture agent have given contradictory results. We show that the re is an antagonist present in normal human serum which inhibits the bindin g of active TGF-beta to the extracellular domain of the TGF-beta type II re ceptor when it is coated on the well of an ELISA plate. This antagonist act ivity is due to a pool of immunoglobulins of the G2, D and M classes. Moreo ver, we show that this same pool of immunoglobulins also recognizes the ext racellular domain of the platelet-derived growth factor alpha-receptor, ins ulin-like growth factor-1 receptor and interleukin-3 receptor, by serial tr ansfer of serum over the different receptors. In addition, the same immunog lobulin pool inhibits the binding of platelet-derived growth factor-AA to i ts receptor, in an analogous way to the inhibition of binding of TGF-beta t o its type II receptor. Circumstantial evidence suggests that the pool of i mmunoglobulins is recognizing a carbohydrate residue that is attached to th e protein when it is synthesized by the mouse myeloma cell line, NSO, in wh ich it is made. If the cytokine receptors are similarly glycosylated in viv o, then the presence of these antibodies in normal human serum may modulate physiological cytokine signalling.