Test of a theory relating to the cross-linking of IgE antibody on the surface of human basophils.
Recent mathematical models of bivalent hapten-induced histamine release from basophils predict that under appropriate conditions histamine release is maximum when cross-link formation is maximum, at a hapten concentration equal to 1/(2Ka), where Ka is the average affinity constant of the hapten for a single IgE binding site. To test this prediction we sensitized human basophils with a monoclonal anti-dinitrophenol IgE and generated histamine release dose-response curves with a bivalent hapten, alpha, epsilon-DNP-lysine. The monoclonal IgE has a published affinity constant of 7.1 X 10(7) M-1 for epsilon-DNP-lysine as determined by equilibrium dialysis. From the position of the maximum of the histamine dose-response curves, both in the presence and in the absence of monovalent DNP hapten, we determine that the sensitizing IgE has an intrinsic affinity constant of 6.9 +/- 0.5 X 10(7) M-1 for epsilon-DNP-lysine and 1.2 +/- 0.6 X 10(6) M-1 for alpha-DNP-lysine. The agreement between the two estimates of the epsilon-DNP-lysine affinity constant, one from histamine release experiments involving surface bound IgE and one from binding experiments involving IgE free in solution, 1) is consistent with a central prediction of the theory of cross-linking and 2) indicates that the hapten-binding properties of the IgE are unaffected by its being bound to Fc epsilon receptors on the basophil surface.
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DW
MacGlashan
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M
Dembo
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B
Goldstein
D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D004136:Dinitrobenzenes / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006241:Haptens / Q000276:immunology; D006636:Histamine Release; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*
D004136:Dinitrobenzenes; D006241:Haptens; D011947:Receptors, Antigen, B-Cell; D007073:Immunoglobulin E