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^–Ser^267^ sequence of IgG1 is implicated in the binding to FcγRIIb. In addition we found that peptides corresponding to the Arg^255^–Ser^267^, Lys^288^–Ser^298^ or Pro^230^–Val^240^ 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 Arg^255^–Ser^267^ can also be considered as a lead for further functional studies. Copyright © 2004 John Wiley & Sons, Ltd.