Molecular recognition of antibody (IgG) by cellular Fc receptor (FcRI).
Earlier studies from this and other laboratories have provided indirect evidence for the involvement of the C gamma 2 domain of human IgG in the binding of IgG to the high affinity monocyte Fc receptor (FcRI). Two approaches have been used to extend these studies and to further localize the site of interaction on human IgG. Firstly, monoclonal antibodies (MAbs) directed against different epitopes on IgG were assayed for their capacity to inhibit the binding of radiolabelled IgG to human monocytes or U937 cells. The capacity of the MAbs to interact with their respective epitopes on FcR-bound IgG was also studied using indirect radiobinding and immunofluorescence assays. Secondly, a number of IgGs from several different species and fragments of human IgGs were assayed for their ability to inhibit the binding of radiolabelled IgG to human monocytes. The amino acid sequences of those IgGs exhibiting relatively tight, intermediate or weak binding to monocyte FcRs were compared. On the basis of these studies a possible monocyte FcR-binding site on human IgG is postulated, involving the lower hinge region of IgG (residues Leu 234-Ser 239) with possible involvement of the nearby N-proximal bend and two beta-strands (Gly 316-Lys 338).
Burton
D R
DR
Department of Biochemistry, University of Sheffield, U.K.
Jefferis
R
R
Partridge
L J
LJ
Woof
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007142:Immunoglobulin gamma-Chains / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D011817:Rabbits; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D011961:Receptors, Fc; D017452:Receptors, IgG