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

Abstract

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 ¹²⁵I‐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 sites/cell on resting cells with an equilibrium binding constant (K_d) of ∼ 100 pM. Stimulation by anti‐CD3 antibodies causes an up‐regulation of IL 4 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 (K_d ∼ 30 nM, ∼ 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 IL 4 to its receptor is specific, being only inhibited by IL 4 and not by IL 2. 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 IL4 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.