Synthetic Peptides from Mouse Fc Receptor (MoFcγRII) That Alter the Binding of IgG to MoFcγRII

Publisher Website
Google Scholar
Abstract
Fc receptors are transmembrane proteins, found on the surfaces of immune cells, that aid in the removal of foreign pathogens by binding to antibody-coated targets via the Fc regions of the antibodies. Using peptides synthesized on pins, overlapping dodecapeptides (170) were synthesized to cover the extracellular region of the mouse Fc receptor for IgG, moFcγRII. The peptides were screened for antibody binding activity by using multivalent immune complexes composed of anti-dinitrophenyl monoclonal mouse IgG1 (ANO6) and dinitrophenyl conjugated to human serum albumin (DNP-HSA). Assays were also carried out with an anti-moFcγRII monoclonal rat IgG (2.4G2). The peptides that interacted with these antibodies prompted the synthesis of two soluble peptides: peptide A [FcγRII-(108−119), RCHSWRNKLLNRamide] and peptide B [FcγRII-(153−165), CKGSLGRTLHQSKamide]. Monomeric S-alkylated (A, B), homodimeric (AA, BB), heterodimeric (AB), and scrambled homodimeric (CC, DD) forms of these peptides were synthesized and examined for their ability to inhibit immune-complex binding to immobilized soluble FcγRII. Peptides AA and CC completely inhibited immune-complex binding while each of the other peptides partially inhibited binding (AB, 80%; A, 80%; BB, 65%; DD, 64%; B, 52%). The pair of monomeric moFcγRII peptides and the set of five dimeric peptides showed the same increase in binding inhibition with increasing net positive charge per residue. These results suggest that the Fc region of IgG binds to the solvent-exposed B/C and F/G loops of the moFcγRII receptor through predominantly electrostatic forces.