Synthesis and receptor binding of IgG1 peptides derived from the IgG Fc region

Katalin Uray, David Medgyesi, Ágnes Hilbert, Gabriella Sármay, János Gergely, Ferenc Hudecz

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The IgG binding Fcγ receptors (FcγRs) play a key role in defence against pathogens by linking humoral and cell-mediated immune responses. Impaired expression and/or function of FcγR may result in the development of pathological autoimmunity. Considering the functions of FcγRs, they are potential target molecules for drug design to aim at developing novel anti-inflammatory and immunomodulatory therapies. Previous data mostly obtained by X-ray analysis of ligand-receptor complexes indicate the profound role of the CH2 domain in binding to various FcγRs. Our aim was to localize linear segments, which are able to bind and also to modulate the function of the low affinity FcγRs, like FcγRIIb and FcγRIIIa. To this end a set of overlapping octapeptides was prepared corresponding to the 231-298 sequence of IgG1 CH2 domain and tested for binding to human recombinant soluble FcγRIIb. Based on these results, a second group of peptides was synthesized and their binding properties to recombinant soluble FcγRIIb, as well as to FcγRs expressed on the cell surface, was investigated. Here we report that peptide representing the Arg 255-Ser267 sequence of IgG1 is implicated in the binding to FcγRIIb. In addition we found that peptides corresponding to the Arg255-Ser267, Lys288-Ser298 or Pro230-Val240 when presented in a multimeric form conjugated to branched chain polypeptide in uniformly oriented copies induced the release of TNFα, a pro-inflammatory cytokine from MonoMac monocyte cell line. These findings indicate that these conjugated peptides are able to cluster the activating FcγRs, and mediate FcγR dependent function. Peptide Arg255-Ser267 can also be considered as a lead for further functional studies.

Original languageEnglish
Pages (from-to)95-105
Number of pages11
JournalJournal of Molecular Recognition
Volume17
Issue number2
DOIs
Publication statusPublished - Mar 1 2004

Keywords

  • Fc receptor binding
  • IgG Fc peptides
  • Overlapping synthetic peptides
  • Solution conformation

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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