Abstract
We describe the gluten T-cell response of a DR7DQ2/DR9DQ9 heterozygous celiac disease patient (CD555). Interestingly, this patient had T cells recognizing gluten in the context of human leukocyte antigen (HLA) molecules of both haplotypes. For the DR9DQ9 haplotype, DQ9 was identified as the antigen-presenting molecule. As DQ9 carries aspartate at DQ β57 but is otherwise identical to DQ8 and not considered associated with celiac disease, we aimed to characterize this DQ9-restricted T-cell response in detail. By fractionation of pepsin-trypsin digested gliadin we identified an epitope stimulatory for several T-cell clones. This epitope was identical to an epitope (DQ8-glut-1) previously identified in DQ8 patients. In CD555, this was the dominant DQ9-restricted epitope, whereas no T-cell response was found toward two other DQ8-restricted epitopes. These findings correlated with peptide binding data demonstrating that this epitope bound better to DQ9 than the two other DQ8-restricted epitopes. Although glutamine to glutamate exchange at P9 improved binding of all three epitopes to DQ8, no such effect was observed for DQ9. The differential ability of DQ8 and DQ9 to harness a negatively charged anchor at P9 may result in fewer potent...Continue Reading
References
Nov 1, 1992·Human Immunology·A SpurklandE Thorsby
Oct 15, 1987·Nature·J A ToddH O McDevitt
Dec 1, 1994·Human Immunology·K E LundinL M Sollid
Mar 1, 1996·The Journal of Experimental Medicine·W W KwokD M Koelle
Oct 7, 1997·Scandinavian Journal of Immunology·O MolbergK E Lundin
Jun 12, 1998·Nature Medicine·O MolbergL M Sollid
Aug 5, 2000·International Immunology·A K MoustakasG K Papadopoulos
Mar 26, 2003·Human Immunology·Kati KarellUNKNOWN European Genetics Cluster on Celiac Disease
Sep 17, 2003·Tissue Antigens·W KlitzM Fernandez-Viña
Aug 16, 2005·Gut·R P AndersonA V S Hill
Nov 8, 2006·Gastroenterology·UNKNOWN AGA Institute
Feb 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Melinda RákiLudvig M Sollid
Jul 17, 2007·Immunity·Kate N HendersonRobert P Anderson
Sep 1, 2009·Nature Immunology·Lars-Egil FallangLudvig M Sollid
Mar 9, 2011·Bioorganic & Medicinal Chemistry·Ulrike JüseLudvig M Sollid
Citations
Apr 27, 2012·Seminars in Immunopathology·Shuo-Wang QiaoLudvig M Sollid
Jun 27, 2012·Seminars in Immunopathology·Frits Koning
Apr 24, 2013·Journal of Clinical Immunology·Nils VenhoffJens Thiel
May 8, 2014·Autoimmune Diseases·Reidun StenbergDaniel Aeschlimann
Jun 11, 2015·Best Practice & Research. Clinical Gastroenterology·Ilma R Korponay-SzabóValentina Discepolo
Jun 13, 2015·Gastroenterology Research and Practice·N OntiverosF Cabrera-Chavez
Sep 28, 2016·Scandinavian Journal of Clinical and Laboratory Investigation·Sandra Aguayo-PatrónAna María Calderón de la Barca
May 9, 2019·Genetic Testing and Molecular Biomarkers·Maxine D RouvroyeHetty J Bontkes
Oct 27, 2015·Medicine·Hongling WangBing Xia
May 4, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yann-Jinn LeeThung-S Lai
Mar 28, 2020·United European Gastroenterology Journal·Jason A Tye-DinRobert P Anderson
Jun 13, 2020·Pflügers Archiv : European journal of physiology·Florian LangKarl S Lang
Sep 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Siri DørumLudvig M Sollid
May 5, 2020·Alimentary Pharmacology & Therapeutics·Chunyan ZhouHongbing Chen
Dec 2, 2020·Pediatric Diabetes·Mara Cerqueiro BybrantAnnelie Carlsson
May 19, 2021·Journal of the European Academy of Dermatology and Venereology : JEADV·A GörögM Sárdy
Jun 19, 2017·Gastroenterology·Katharina Julia WerkstetterUNKNOWN ProCeDE study group
Oct 7, 2021·BMC Medicine·Fernando Fernández-BañaresConcepción Núñez