Identification of interleukin 4 receptor-associated proteins and expression of both high- and low-affinity binding on human lymphoid cells.

Interleukin 4 (IL4) 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 125I-IL4 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 IL4 binding sites/cell on resting cells with an equilibrium binding constant (Kd) of approximately 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 approximately 30 nM, approximately 9000 sites/cell) is expressed on resting lymphocytes. The number of low-affinity binding sites for IL 4 also increases twofold upon cell activation. Exogenous IL 4 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 IL 4 and not by IL2. By contrast, the gibbon leukemia cell line MLA 144 expresses only high-affinity receptors for IL4. 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 IL4 is discussed.