Chimeric Fc receptors identify immunoglobulin‐binding regions in human FcγRII and FcϵRI

Mark D. Hulett, Ian F C McKenzie, P. Mark Hogarth

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47 Citations (Scopus)

Abstract

FcγRII and FcϵRI are functionally distinct cell surface receptors for immunoglobulin (Ig); FcγRII binds IgG with low affinity, whereas FcϵRI binds IgE with high affinity, yet they are homologous in structure and sequence having extracellular regions containing two Ig‐like domains with 38% amino acid identity. Chimeric receptors derived from human FcγRII and FcγRI were produced by exchanging homologous regions of the two receptors to define binding region(s) for IgG in FcγRII and IgE in FcϵRI. Firstly, a chimeric form of the FcϵRI α chain was produced by replacing the transmembrane region and cytoplasmic tail with that of FcγRII. This mutant α chain could be expressed on the cell surface independently of associated β and γ subunits, and retained high‐affinity IgE binding, indicating that the extracellular region of the FcγRI α chain is sufficient for high‐affinity IgE binding. Secondly, to identify the role of the individual domains in Fc binding of both FcγRII and FcγRI, chimeric receptors were generated by exchanging the first extracellular domains between FcγRII and the α chain mutant and used to demonstrate that the second extracellular domain of both receptors contains region(s) directly involved in Ig binding. Additional chimeric receptors were constructed to localize the Ig interactive regions in domain two of FcγRII and FcγRI; these identified a single region of IgG binding in FcγRII located between residues Ser136 to Val169, and at least three independent IgE binding regions in the FcγRI α chain, between residues Trp87 to Lys128, Tyr129 to Asp145, and Ser146 to Val169.

Original languageEnglish
Pages (from-to)640-645
Number of pages6
JournalEuropean Journal of Immunology
Volume23
Issue number3
DOIs
Publication statusPublished - 1 Jan 1993
Externally publishedYes

Keywords

  • Cell surface receptors
  • FcR active sites
  • FcγRII
  • FcϵRI
  • Immunoglobulin binding

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