Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain.
We used mapping with synthetic overlapping peptides in combination with molecular modeling to analyze the IgG antibodies that humans naturally produce against human T-cell receptor beta chains and to localize the recognized peptide autoantigens in the three-dimensional structure of the molecule. Healthy individuals produce low levels of antibodies against T-cell receptor peptides, and these can be increased in autoimmune diseases. We characterized the reactivities in detail because IgG molecules reactive with self peptides occur in preparations of intravenous immunoglobulin and can be isolated by immunoaffinity chromatography. Natural IgG antibodies were directed against three major peptides. One corresponds to the first complementarity-determining region of the variable region. A second corresponds to the third framework of the variable region. The third is located in the constant region and is predicted to be a loop that extends out of the beta-barrel structure. This peptide is one that would give a characteristic structural distinction between the beta-chain constant region and the constant regions of immunoglobulin light chains to which beta chains are homologous. The capacity to bind these peptides is found in small fractions of normal polyclonal IgG, which contains both kappa chains and lambda chains. The activity is antibody-like in being confined to the Fab fragment and in its capacity to discriminate among homologous synthetic peptides corresponding to distinct beta-chain variable-region genes. We propose that a recognition and regulatory process naturally occurs that parallels the immune network for the regulation of the production of antibodies.
Marchalonis
J J
JJ
Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson 85724.
Kaymaz
H
H
Dedeoglu
F
F
Schluter
S F
SF
Yocum
D E
DE
Edmundson
A B
AB
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D010455:Peptides; D011948:Receptors, Antigen, T-Cell