FceRI binding affinity

Omalizumab, a recombinant humanized monoclonal antibody that inhibits the binding of human IgE to its high-affinity receptor FceRI by selectively binding the immunoglobulin in solution, has been used as a successful treatment of intractable allergic asthma. The efficacy of the monoclonal antibody treatment was therefore investigated in patients with chronic autoimmune urticaria who remained symptomatic on antihistamine therapy. Of the 12 patients treated, seven showed complete resolution of the urticaria, four responded with a decrease in the urticaria activity score but the urticaria persisted, and one patient showed no improvement. 

The initial event in the activation of mast cells for mediator release is the binding of IgE antibodies to the high-affinity 10 M) FceRI IgE receptor abundantly expressed on the mast cell and basophil surfaces. 

Hakimi J, Seals C, Kondas JA, Pettine L, Danho W, Kochan J. The a subunit of the human IgE receptor (FcERI) is sufficient for high affinity IgE binding. J Biol Chem 1990 265 22079-22081. 

Hulett MD, Brinkworth RI, C. McKenzie IF, Hogarth PM. Fine structure analysis of interaction of FceRI with IgE. J Biol Chem 1999 274 13345—13352. McDonnell JM, BeavU AJ, Mackay GA, Jameson BA, Komgold R, Gould HJ, Sutton BJ. Structure based design and characterization of peptides that inhibit IgE binding to its high-affinity receptor. Nature Struct Biol 1996 3 419—425. 

Henry AJ, Cook JPD, McDonneU JM, Mackay GA, Shi J, Sutton BJ, Gould HJ. Participation of the N-terminal region of Ce3 in the binding of human IgE to its high-affinity receptor FceRI. Biochemistry 1997 36 15568-15578. 

IgE receptors bind either to the Fc portion of the immunoglobulin, and thus belong to the Fc receptor superfamily, or to carbohydrate moieties. The high-affinity receptor (FceRI) and the low-affinity receptor (FceRII/CD23) fall in the first group, while, Mac2/galectin-3, a member of the S-type lectin family, falls in the second one. 

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