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Identification of the High Affinity Receptor Binding Region in Human Immunoglobulin E

1996; Elsevier BV; Volume: 271; Issue: 13 Linguagem: Inglês

10.1074/jbc.271.13.7494

1083-351X

Birgit A. Helm, Ian Sayers, Adrian Higginbottom, Denise Cantarelli Machado, Yan Ling, Khalid Ahmad, Eduardo A. Padlan, Anne Wilson,

Glycosylation and Glycoproteins Research

We have investigated the capacity of N- and C-terminally truncated and chimeric human (h) IgE-derived peptides to inhibit the binding of 125 I-labeled hIgE, and to engage cell lines expressing high and low affinity receptors (FcεRI/II). The peptide sequence Pro 343 -Ser 353 of the hCε3 domain is common to all hε-chain peptides that recognize hFcεRI. This region in IgE is homologous to the A loop in Cγ2 that engages the rat neonatal IgG receptor. Optimum FcεRI occupancy by hIgE occurs at pH 6.4, with a second peak at 7.4. N- or C-terminal truncation has little effect on the association rate of the ligands with this receptor. Dissociation markedly increases following C-terminal deletion, and hFcεRI occupancy at pH 6.4 is diminished. His residue(s) in the C-terminal region of the ε-chain may thus contribute to the high affinity of interaction. Grafting the homologous rat ε-chain sequence into hIgE maintains hFcεRI interaction without conferring binding to rat FcεRI. hFcεRII interaction is lost, suggesting that these residues also contribute to hFcεRII binding. hε-chain peptides comprising only this sequence do not block hIgE/hFcεRI interaction or engage the receptor. Therefore, sequences N- or C-terminal to this core peptide provide structures necessary for receptor recognition.