Localization of the Discontinuous Immunodominant Region Recognized by Human Anti-thyroperoxidase Autoantibodies in Autoimmune Thyroid Diseases
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,...
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| Veröffentlicht in: | The Journal of biological chemistry 2003-03, Vol.278 (11), p.9560-9569 |
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| container_title | The Journal of biological chemistry |
| container_volume | 278 |
| creator | Bresson, Damien Cerutti, Martine Devauchelle, Gérard Pugnière, Martine Roquet, Francoise Bes, Cédric Bossard, Carine Chardès, Thierry Péraldi-Roux, Sylvie |
| description | 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, L X PE X D, QSYP, and E X (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 353â363, 377â386, and 713â720 from the myeloperoxidase-like domain and region
766â775 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 âmini-TPOâ as a target autoantigen or designing therapeutic peptides able to
block undesired autoimmune responses. |
| doi_str_mv | 10.1074/jbc.M211930200 |
| format | Article |
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a major autoantigen in autoimmune thyroid diseases, has not yet been completely localized. By using peptide phage-displayed
technology, we identified three critical motifs, L X PE X D, QSYP, and E X (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 353â363, 377â386, and 713â720 from the myeloperoxidase-like domain and region
766â775 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 âmini-TPOâ as a target autoantigen or designing therapeutic peptides able to
block undesired autoimmune responses.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M211930200</identifier><identifier>PMID: 12501244</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Alanine - chemistry ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Antibodies - chemistry ; Antibodies, Monoclonal - metabolism ; Autoantibodies - chemistry ; Autoimmune Diseases - immunology ; B-Lymphocytes - metabolism ; Binding, Competitive ; Blotting, Western ; Cell Line ; Cell Membrane - metabolism ; Cloning, Molecular ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Immunologic ; Enzyme-Linked Immunosorbent Assay ; Epitopes ; Graves Disease - immunology ; Graves Disease - metabolism ; Humans ; Immunoassay ; Immunodominant Epitopes ; Insecta ; Iodide Peroxidase - chemistry ; Iodide Peroxidase - immunology ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation ; Peptide Library ; Peptides - chemistry ; Protein Binding ; Protein Denaturation ; Protein Structure, Tertiary ; Recombinant Proteins - chemistry ; Sequence Homology, Amino Acid ; Thyroid Diseases - immunology</subject><ispartof>The Journal of biological chemistry, 2003-03, Vol.278 (11), p.9560-9569</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-6380dbb82fbf65084dff766d83dae5027447bc52cbddb7096fd3b60781143d353</citedby><cites>FETCH-LOGICAL-c390t-6380dbb82fbf65084dff766d83dae5027447bc52cbddb7096fd3b60781143d353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12501244$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bresson, Damien</creatorcontrib><creatorcontrib>Cerutti, Martine</creatorcontrib><creatorcontrib>Devauchelle, Gérard</creatorcontrib><creatorcontrib>Pugnière, Martine</creatorcontrib><creatorcontrib>Roquet, Francoise</creatorcontrib><creatorcontrib>Bes, Cédric</creatorcontrib><creatorcontrib>Bossard, Carine</creatorcontrib><creatorcontrib>Chardès, Thierry</creatorcontrib><creatorcontrib>Péraldi-Roux, Sylvie</creatorcontrib><title>Localization of the Discontinuous Immunodominant Region Recognized by Human Anti-thyroperoxidase Autoantibodies in Autoimmune Thyroid Diseases</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>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, L X PE X D, QSYP, and E X (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 353â363, 377â386, and 713â720 from the myeloperoxidase-like domain and region
766â775 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 âmini-TPOâ as a target autoantigen or designing therapeutic peptides able to
block undesired autoimmune responses.</description><subject>Alanine - chemistry</subject><subject>Amino Acid Motifs</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies - chemistry</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Autoantibodies - chemistry</subject><subject>Autoimmune Diseases - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>Binding, Competitive</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Cell Membrane - metabolism</subject><subject>Cloning, Molecular</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dose-Response Relationship, Immunologic</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epitopes</subject><subject>Graves Disease - immunology</subject><subject>Graves Disease - metabolism</subject><subject>Humans</subject><subject>Immunoassay</subject><subject>Immunodominant Epitopes</subject><subject>Insecta</subject><subject>Iodide Peroxidase - chemistry</subject><subject>Iodide Peroxidase - immunology</subject><subject>Kinetics</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutation</subject><subject>Peptide Library</subject><subject>Peptides - chemistry</subject><subject>Protein Binding</subject><subject>Protein Denaturation</subject><subject>Protein Structure, Tertiary</subject><subject>Recombinant Proteins - chemistry</subject><subject>Sequence Homology, Amino Acid</subject><subject>Thyroid Diseases - immunology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkU2LFDEQhoMo7uzq1aMEBG89VpL-SB-HVXcXRoRlBW8hH9XTWaaTsdONzv4If7NpZ2DrUlA871tUvYS8Y7Bm0JSfHo1df-OMtQI4wAuyYiBFISr28yVZAXBWtLySF-QypUfIVbbsNblgvALGy3JF_m6j1Xv_pCcfA40dnXqkn32yMUw-zHFO9G4Y5hBdHHzQYaL3uFvQe7RxF_wTOmqO9HYedKCbrCmm_jjGA47xj3c6Id3MU8w6b6LzmKgP_yd-MUX6sMDeLRsxw-kNedXpfcK3535Ffnz98nB9W2y_39xdb7aFFS1MRS0kOGMk70xXVyBL13VNXTspnMYKeFOWjbEVt8Y500Bbd06YGhrJWCmcqMQV-XjyPYzx14xpUkO-Gfd7HTDfrJisWwkNy-D6BNoxpjRipw6jH_R4VAzUkoDKCajnBLLg_dl5NgO6Z_z88gx8OAG93_W__YjK-Gh7HBRvpGJMtVUN4h87jJEE</recordid><startdate>20030314</startdate><enddate>20030314</enddate><creator>Bresson, Damien</creator><creator>Cerutti, Martine</creator><creator>Devauchelle, Gérard</creator><creator>Pugnière, Martine</creator><creator>Roquet, Francoise</creator><creator>Bes, Cédric</creator><creator>Bossard, Carine</creator><creator>Chardès, Thierry</creator><creator>Péraldi-Roux, Sylvie</creator><general>American Society for Biochemistry and Molecular Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20030314</creationdate><title>Localization of the Discontinuous Immunodominant Region Recognized by Human Anti-thyroperoxidase Autoantibodies in Autoimmune Thyroid Diseases</title><author>Bresson, Damien ; Cerutti, Martine ; Devauchelle, Gérard ; Pugnière, Martine ; Roquet, Francoise ; Bes, Cédric ; Bossard, Carine ; Chardès, Thierry ; Péraldi-Roux, Sylvie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-6380dbb82fbf65084dff766d83dae5027447bc52cbddb7096fd3b60781143d353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Alanine - chemistry</topic><topic>Amino Acid Motifs</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies - chemistry</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Autoantibodies - chemistry</topic><topic>Autoimmune Diseases - immunology</topic><topic>B-Lymphocytes - metabolism</topic><topic>Binding, Competitive</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Cell Membrane - metabolism</topic><topic>Cloning, Molecular</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dose-Response Relationship, Immunologic</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epitopes</topic><topic>Graves Disease - immunology</topic><topic>Graves Disease - metabolism</topic><topic>Humans</topic><topic>Immunoassay</topic><topic>Immunodominant Epitopes</topic><topic>Insecta</topic><topic>Iodide Peroxidase - chemistry</topic><topic>Iodide Peroxidase - immunology</topic><topic>Kinetics</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutation</topic><topic>Peptide Library</topic><topic>Peptides - chemistry</topic><topic>Protein Binding</topic><topic>Protein Denaturation</topic><topic>Protein Structure, Tertiary</topic><topic>Recombinant Proteins - chemistry</topic><topic>Sequence Homology, Amino Acid</topic><topic>Thyroid Diseases - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bresson, Damien</creatorcontrib><creatorcontrib>Cerutti, Martine</creatorcontrib><creatorcontrib>Devauchelle, Gérard</creatorcontrib><creatorcontrib>Pugnière, Martine</creatorcontrib><creatorcontrib>Roquet, Francoise</creatorcontrib><creatorcontrib>Bes, Cédric</creatorcontrib><creatorcontrib>Bossard, Carine</creatorcontrib><creatorcontrib>Chardès, Thierry</creatorcontrib><creatorcontrib>Péraldi-Roux, Sylvie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bresson, Damien</au><au>Cerutti, Martine</au><au>Devauchelle, Gérard</au><au>Pugnière, Martine</au><au>Roquet, Francoise</au><au>Bes, Cédric</au><au>Bossard, Carine</au><au>Chardès, Thierry</au><au>Péraldi-Roux, Sylvie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Localization of the Discontinuous Immunodominant Region Recognized by Human Anti-thyroperoxidase Autoantibodies in Autoimmune Thyroid Diseases</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2003-03-14</date><risdate>2003</risdate><volume>278</volume><issue>11</issue><spage>9560</spage><epage>9569</epage><pages>9560-9569</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>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, L X PE X D, QSYP, and E X (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 353â363, 377â386, and 713â720 from the myeloperoxidase-like domain and region
766â775 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 âmini-TPOâ as a target autoantigen or designing therapeutic peptides able to
block undesired autoimmune responses.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>12501244</pmid><doi>10.1074/jbc.M211930200</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Alanine - chemistry Amino Acid Motifs Amino Acid Sequence Animals Antibodies - chemistry Antibodies, Monoclonal - metabolism Autoantibodies - chemistry Autoimmune Diseases - immunology B-Lymphocytes - metabolism Binding, Competitive Blotting, Western Cell Line Cell Membrane - metabolism Cloning, Molecular Dose-Response Relationship, Drug Dose-Response Relationship, Immunologic Enzyme-Linked Immunosorbent Assay Epitopes Graves Disease - immunology Graves Disease - metabolism Humans Immunoassay Immunodominant Epitopes Insecta Iodide Peroxidase - chemistry Iodide Peroxidase - immunology Kinetics Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Mutation Peptide Library Peptides - chemistry Protein Binding Protein Denaturation Protein Structure, Tertiary Recombinant Proteins - chemistry Sequence Homology, Amino Acid Thyroid Diseases - immunology |
| title | Localization of the Discontinuous Immunodominant Region Recognized by Human Anti-thyroperoxidase Autoantibodies in Autoimmune Thyroid Diseases |
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