Localization of the Discontinuous Immunodominant Region Recognized by Human Anti-thyroperoxidase Autoantibodies in Autoimmune Thyroid Diseases
| Autor: | Carine Bossard, Cédric Bès, Martine Pugnière, Sylvie Peraldi-Roux, Martine Cerutti, Thierry Chardès, Gérard Devauchelle, Damien Bresson, Françoise Roquet |
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| Přispěvatelé: | Institut de Biotechnologie-Pharmacologie, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-BioRad-Centre National de la Recherche Scientifique (CNRS), Biologie Intégrative et Virologie des Insectes [Univ. de Montpellier II] (BIVI), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2), Centre National de la Recherche Scientifique (CNRS), Endocrinologie et communication cellulaire, Institut Louis Bugnard-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse] |
| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Protein Denaturation Insecta Amino Acid Motifs thyroide Biochemistry Epitope Epitopes CELLULE INSECTE MONOCLONAL baculovirus 0302 clinical medicine Cloning Molecular Immunoassay B-Lymphocytes 0303 health sciences Alanine biology Mimotope Chinese hamster ovary cell Thyroid Antibodies Monoclonal food and beverages Graves Disease Recombinant Proteins [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] 3. Good health medicine.anatomical_structure embryonic structures anticorps Antibody Protein Binding endocrine system Blotting Western Molecular Sequence Data Dose-Response Relationship Immunologic Enzyme-Linked Immunosorbent Assay Binding Competitive Iodide Peroxidase Antibodies Autoimmune Diseases Cell Line 03 medical and health sciences Peptide Library Thyroid peroxidase medicine Animals Humans Amino Acid Sequence Peptide library Molecular Biology Autoantibodies 030304 developmental biology maladie autoimmune Dose-Response Relationship Drug Sequence Homology Amino Acid Immunodominant Epitopes Cell Membrane Autoantibody autoimmune Cell Biology Thyroid Diseases Protein Structure Tertiary Kinetics Mutation Immunology Mutagenesis Site-Directed biology.protein Peptides 030215 immunology |
| Zdroj: | Journal of Biological Chemistry 11 (278), 9560-9569. (2003) Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2003, 278 (11), pp.9560-9569. ⟨10.1074/jbc.M211930200⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.m211930200 |
| Popis: | 58 ref.; International audience; The discontinuous immunodominant region (IDR) recognized by autoantibodies directed against the thyroperoxidase (TPO) molecule, a major autoantigen in autoimmune thyroid diseases, has not yet been completely localized. By using peptide phage-displayed technology, we identified three critical motifs, LXPEXD, QSYP, and EX(E/D)PPV, within selected mimotopes which interacted with the human recombinant anti-TPO autoantibody (aAb) T13, derived from an antibody phage-displayed library obtained from thyroid-infiltrating TPO-selected B cells of Graves' disease patients. Mimotope sequence alignment on the TPO molecule, together with the binding analysis of the T13 aAb on TPO mutants expressed by Chinese hamster ovary cells, demonstrated that regions 353–363, 377–386, and 713–720 from the myeloperoxidase-like domain and region 766–775 from the complement control protein-like domain are a part of the IDR recognized by the recombinant aAb T13. Furthermore, we demonstrated that these regions were involved in the binding to TPO of sera containing TPO-specific autoantibodies from patients suffering from Hashimoto's and Graves' autoimmune diseases. Identification of the IDR could lead to improved diagnosis of thyroid autoimmune diseases by engineering “mini-TPO” as a target autoantigen or designing therapeutic peptides able to block undesired autoimmune responses. |
| Databáze: | OpenAIRE |
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