COMPLEMENT IMMUNOGLOBULIN INTERACTIONS

Normal circulating immunoglobulin may control complement binding to targets and thereby the manifestations of autoimmune disease. Molecular analysis of IgG and IgM mutants suggests that Clq binding by IgG utilizes a core Clu-X-Lys-X-Lys motif (where X is any amino acid). Additional amino acids, particularly homologous proline residues at position 331 in IgG and 436 in IgM, appear critical for classical pathway initiation. Glycosylation of IgG heavy chain is important in Clq binding, as well as glycosylation of IgA heavy chain for alternative pathway initiation. Additional recent evidence suggests an important role for C3 in antigen presentation. The data also raise the possibility that C3 plays a significant role in the intracellular antigen processing pathway.