Evidence that HLA-DQ9 confers risk to celiac disease by presence of DQ9-restricted gluten-specific T cells

Human Immunology
M BoddLudvig M Sollid

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

Mar 1, 1996·The Journal of Experimental Medicine·W W KwokD M Koelle
Feb 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Melinda RákiLudvig M Sollid
Mar 9, 2011·Bioorganic & Medicinal Chemistry·Ulrike JüseLudvig M Sollid

❮ Previous
Next ❯

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
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
Jun 19, 2017·Gastroenterology·Katharina Julia WerkstetterUNKNOWN ProCeDE study group
Oct 7, 2021·BMC Medicine·Fernando Fernández-BañaresConcepción Núñez

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atrophic Gastritis

Atrophic Gastritis is a process where gastric glandular cells are lost and replaced with firbous tissues, as a result of chronic inflammation. Learn more about Atrophic Gastritis here.