NATURAL IGA-ANTI-F(AB')(2)GAMMA AUTOANTIBODY OCCURRING IN HEALTHY-INDIVIDUALS AND KIDNEY GRAFT RECIPIENTS RECOGNIZES AN IGG1 HINGE REGION EPITOPE

Natural anti-IgG autoantibodies are found both in healthy individuals and in patients with certain diseases, One group of these Abs recogniz es epitopes located in the F(ab')(2) region of the IgG molecule. The i mmunoregulatory role of these Abs in healthy individuals, graft reject ion, and disease was previously studied, usually with a focus on the c haracterization of anti-idiotypic Abs, In the present study, we charac terize the epitope recognized by an anti-F(ab')(2) gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals a nd kidney transplant recipients, The autoantibody described herein rea cts strongly with F(ab')(2) gamma but only poorly with Fab gamma fragm ents, a binding pattern pointing to an epitope located in the hinge re gion, Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structur al analyses of peptide constructs showed that a defined conformation o f the first three residues of the lower hinge is required for a full e xpression of the epitope, Binding of IgA to the hinge region of IgG1 c overs part of the physiologically active Pc domain, immobilizes the Fa b arms, and thereby can be expected to exert immunoregulatory function s.