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.
Foxwell
B M
BM
Drug Safety Assessment Sandoz Ltd., Basel, Switzerland.
Woerly
G
G
Ryffel
B
B
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D002460:Cell Line; D006801:Humans; D006922:Hylobates; D015847:Interleukin-4 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008970:Molecular Weight; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4