Identification of interleukin 4 receptor-associated proteins and expression of both high-and low-affinity binding on human lymphoid cells
Drug Safety Assessment Sandoz Ltd., Basel Interleukin 4 (IL 4) produced by activated T cells expresses its biological effects on T and B lymphocytes by binding to specific membrane receptors. Cross-linking of human recombinant '"I-IL 4 to peripheral blood mononuclear cells identifies a trimolecular complex consisting of a 65/70-kDa doublet and a 110-kDa protein.
Scatchard analysis reveals about 300 IL 4 binding sitedcell on resting cells with an equilibrium binding constant (Kd) of -100 PM. Stimulation by anti-CD3 antibodies causes an up-regulation of IL4 receptors by a factor of 2 to 3 without any change in binding affinity. In addition to this high-affinity binding site a second class of a previously unidentified, low-affinity receptor (Kd -30 nM, -9000 siteskell) is expressed on resting lymphocytes. The number of low-affinity binding sites for IL 4 also increases twofold upon cell activation. Exogenous IL4 enhances the expression of its receptor on resting lymphocytes and this effect is further increased by anti-CD3 activation. Binding of IL4 to its receptor is specific, being only inhibited by IL4 and not by IL2. By contrast, the gibbon leukemia cell line MLA 144 expresses only high-affinity receptors for IL 4. Cross-linking studies reveal a 45/50-kDa IL 4 receptor-associated doublet in addition to the three proteins identified in human peripheral blood mononuclear cells. The functional significance of the different proteins composing the receptor for IL 4 is discussed.