Synthetic peptides from mouse Fc receptor (MoFc gamma RII) that alter the binding of IgG to MoFc gamma RII.
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, moFc gamma RII. 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-moFc gamma RII monoclonal rat IgG (2.4G2). The peptides that interacted with these antibodies prompted the synthesis of two soluble peptides: peptide A [Fc gamma RII-(108-119), RCHSWRNKLLNRamide] and peptide B [Fc gamma RII-(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 Fc gamma RII. 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 moFc gamma RII 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 moFc gamma RII receptor through predominantly electrostatic forces.
Goldsmith
E B
EB
Department of Chemistry, University of North Carolina, Chapel Hill 27599-3290, USA.
Erickson
B W
BW
Thompson
N L
NL
D000595:Amino Acid Sequence; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017452:Receptors, IgG / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D055672:Static Electricity
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D009842:Oligopeptides; D010446:Peptide Fragments; D017452:Receptors, IgG; D011994:Recombinant Proteins