Cross-linking of interleukin 4 to surface molecules on murine T and B lymphocytes.
Interleukin 4 (IL-4) is a T-cell derived lymphokine with multiple activities on a variety of cells. An intriguing feature of the different IL-4-mediated activities is their requirements for markedly different concentrations of IL-4 even on the same cell population. To gain some insight into the phenomenon, we have analyzed the structure of IL-4-binding proteins on T and B cells by cross-linking different concentrations of 125I-labeled IL-4 (125I-IL-4) to cells. Cross-linking of 125I-IL-4 at relatively low concentrations in the presence of the cross-linking agent 3,3'-dithiobis(propionic acid hydroxysuccinimide ester) resulted in the detection of the previously described 60- to 75-kDa protein. At higher 125I-IL-4 concentrations, however, an additional molecule of 105 kDa was observed. Cross-linking of 125I-IL-4 to both molecules was specific; it was inhibited by the presence of a 50-fold excess of either unlabeled IL-4 or monoclonal anti-IL-4 antibody. Furthermore, considerable size heterogeneity of the IL-4-binding proteins was evident in different cell populations. These results suggest that IL-4 receptors might have a more complex structure than originally reported and/or that high concentrations of IL-4 might induce interactions of the previously described IL-4 receptor (60-75 kDa) with a 105-kDa molecule. Hence, it is possible that IL-4 might generate a different signal at high concentrations through interaction of its receptor with another membrane molecule.
Fernandez-Botran
R
R
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Uhr
J W
JW
Vitetta
E S
ES
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003432:Cross-Linking Reagents / Q000378:metabolism*; D005260:Female; D015847:Interleukin-4; D007378:Interleukins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D013388:Succinimides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D003432:Cross-Linking Reagents; D007378:Interleukins; D007457:Iodine Radioisotopes; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D013388:Succinimides; D015847:Interleukin-4; C011240:dithiobis(succinimidylpropionate)