Human Autoantibodies Reactive with Synthetic Autoantigens from T-Cell Receptor β Chain

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 8; pp. 3325 - 3329
• Main Authors: Marchalonis, John J., Kaymaz, Hulya, Dedeoglu, Fatma, Schluter, Samuel F., Yocum, David E., Edmundson, Allen B.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.04.1992; National Acad Sciences
• Subjects: Adult; Aged; Amino Acid Sequence; Antibodies; Antigens; Arthritis, Rheumatoid - immunology; Autoantibodies; Autoantibodies - analysis; Autoantibodies - immunology; Autoantigens; Autoantigens - immunology; Autoimmunity (experimental aspects and models); Biological and medical sciences; Enzyme linked immunosorbent assay; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunoglobulin constant regions; Immunoglobulin G - chemistry; Immunoglobulin G - immunology; Immunoglobulin G - isolation & purification; Immunoglobulins; Immunology; Lupus Erythematosus, Systemic - immunology; Macromolecular Substances; Male; Middle Aged; Models, Molecular; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - immunology; Protein Conformation; Reactivity; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; T cell antigen receptors; Autoimmunity; Human; Autoantigen; T cell receptor; Peptides; Constant region; Variable region; Beta-Peptide chain; Autoantibody; IgG; Recognition; Idiotype
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.8.3325

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 β 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 β-barrel structure. This peptide is one that would give a characteristic structural distinction between the β-chain constant region and the constant regions of immunoglobulin light chains to which β chains are homologous. The capacity to bind these peptides is found in small fractions of normal polyclonal IgG, which contains both κ chains and λ 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 β-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.