Inhibition of C1-mediated immune hemolysis by monomeric and dimeric peptides from the second constant domain of human immunoglobulin G.
Activation of the classical complement cascade by immunoglobulin G involves binding of the first complement component (C1) to a multivalent antigen-IgG complex. Binding occurs by interaction of a site on the surface of the C gamma 2 domain of IgG with a globular head of the C1q subcomponent of C1. Previously we found that the synthetic decapeptide consisting of residues 281-290 from the second constant domain of the gamma-chain of the human IgG1 protein Eu inhibited the binding of human C1 to sensitized erythrocytes. The present study describes inhibition of monomeric and dimeric peptides containing residues 289-292 or 282-292: (formula: see text). On a molar basis, monomeric peptide 282-292 is just as active an inhibitor of C1 binding as peptide 281-290, whereas monomeric peptide 289-292 (tuftsin) is 4 times less active. Peptides 282-292 and 289-292 were each cross-linked at the amino terminus through terephthaloyl-bis(iminodiacetic acid) (Tid). Each dimeric peptide is twice as active on a molar basis as the corresponding monomeric peptide. Dimeric peptide Tid(282-292)2 is just as active on a molar basis as the monomeric 7S form of human IgG1 and 60% as active as the Fc fragment of IgG in inhibiting the binding of human C1 to sensitized erythrocytes. These results suggest that the positively charged residues His-285, Lys-288, Lys-290, and Arg-292, which are located on the outer surface of the C gamma 2 domain, may be involved in the C1q-binding site of human IgG.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003172:Complement C1 / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007136:Immunoglobulins; D046911:Macromolecular Substances; D010455:Peptides / Q000276:immunology*; D011817:Rabbits; D012756:Sheep
D003172:Complement C1; D003432:Cross-Linking Reagents; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007136:Immunoglobulins; D046911:Macromolecular Substances; D010455:Peptides; D002118:Calcium