A natural IgA-anti-F(ab')2gamma 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 recognizes epitopes located in the F(ab')2 region of the IgG molecule. The immunoregulatory role of these Abs in healthy individuals, graft rejection, and disease was previously studied, usually with a focus on the characterization of anti-idiotypic Abs. In the present study, we characterize the epitope recognized by an anti-F(ab')2gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals and kidney transplant recipients. The autoantibody described herein reacts strongly with F(ab')2gamma but only poorly with Fab(gamma) fragments, a binding pattern pointing to an epitope located in the hinge region. Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structural analyses of peptide constructs showed that a defined conformation of the first three residues of the lower hinge is required for a full expression of the epitope. Binding of IgA to the hinge region of IgG1 covers part of the physiologically active Fc domain, immobilizes the Fab arms, and thereby can be expected to exert immunoregulatory functions.
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Germany.
P
P
Terness
D
D
Navolan
L
L
Moroder
F
F
Siedler
E
E
Weyher
I
I
Kohl
C
C
Dufter
M
M
Welschof
D
D
Drugarin
F
F
Schneider
G
G
Opelz
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001667:Binding, Competitive; D002942:Circular Dichroism; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D014660:Vasoactive Intestinal Peptide / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D000939:Epitopes; D007070:Immunoglobulin A; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D010446:Peptide Fragments; D014660:Vasoactive Intestinal Peptide