{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:56:48Z","timestamp":1787839008795,"version":"build-2784847793"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"crossref","award":["ERC-2010-Ad-268541"],"award-info":[{"award-number":["ERC-2010-Ad-268541"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Council of Norway, Center of Excellence Funding Scheme","award":["179573\/V40"],"award-info":[{"award-number":["179573\/V40"]}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","award":["832\/16"],"award-info":[{"award-number":["832\/16"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"name":"European Community\u2019s Seventh Framework Program","award":["BioStruct-X (grant 283570)"],"award-info":[{"award-number":["BioStruct-X (grant 283570)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,7]]},"abstract":"<jats:p>\n                    The role of B cells and posttranslational modifications in pathogenesis of organ-specific immune diseases is increasingly envisioned but remains poorly understood, particularly in human disorders. In celiac disease, transglutaminase 2\u2013modified (TG2-modified; deamidated) gluten peptides drive disease-specific T cell and B cell responses, and antibodies to deamidated gluten peptides are excellent diagnostic markers. Here, we substantiate by high-throughput sequencing of\n                    <jats:italic>IGHV<\/jats:italic>\n                    genes that antibodies to a disease-specific, deamidated, and immunodominant B cell epitope of gluten (PLQPEQPFP) have biased and stereotyped usage of\n                    <jats:italic>IGHV3-23<\/jats:italic>\n                    and\n                    <jats:italic>IGHV3-15<\/jats:italic>\n                    gene segments with modest somatic mutations. X-ray crystal structures of 2 prototype\n                    <jats:italic>IGHV3-15\/IGKV4-1<\/jats:italic>\n                    and\n                    <jats:italic>IGHV3-23\/IGLV4-69<\/jats:italic>\n                    antibodies reveal peptide interaction mainly via germline-encoded residues. In-depth mutational analysis showed restricted selection and substitution patterns at positions involved in antigen binding. While the\n                    <jats:italic>IGHV3-15\/IGKV4-1<\/jats:italic>\n                    antibody interacts with Glu5 and Gln6, the\n                    <jats:italic>IGHV3-23\/IGLV4-69<\/jats:italic>\n                    antibody interacts with Gln3, Pro4, Pro7, and Phe8 \u2014 residues involved in substrate recognition by TG2. Hence, both antibodies, despite different interaction with the epitope, recognize signatures of TG2 processing that facilitates B cell presentation of deamidated gluten peptides to T cells, thereby providing a molecular framework for the generation of these clinically important antibodies. The study provides essential insight into the pathogenic mechanism of celiac disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.93961","type":"journal-article","created":{"date-parts":[[2017,8,16]],"date-time":"2017-08-16T11:00:52Z","timestamp":1502881252000},"source":"Crossref","is-referenced-by-count":34,"title":["Stereotyped antibody responses target posttranslationally modified gluten in celiac disease"],"prefix":"10.1172","volume":"2","author":[{"given":"Omri","family":"Snir","sequence":"first","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital\u2013Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital\u2013Rikshospitalet, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moriah","family":"Gidoni","sequence":"additional","affiliation":[{"name":"Bioengineering Faculty of Engineering, Bar-Ilan University, Ramt Gan, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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