Investigating celiac disease using recombinant soluble MHC class II molecules
Year: 2009
Type: dissertation
Abstract: Celiac disease (CD) is a chronic intestinal inflammation showing a strong association to HLA-DQ2.5. This thesis focused on the use of soluble MHC class II tetramers to examine the underlying mechanism for this selective CD association and also to develop a potential diagnostic tool based on the detection of gluten specific T cells. \n\nDQ2.5 is associated with atypically high amounts of Ii-chain derived CLIP peptides. This phenotype was assigned to an abnormally low interaction with the peptide editing molecule HLA-DM, and high kinetic stability of CLIP peptides to DQ2.5. HLA-DQ2.2 is a highly similar molecule, but does not show strong CD association. Interestingly, this molecule displayed a CLIP low phenotype due to a drastically reduced kinetic stability for CLIP. This was assigned to a polymorphic residue causing the gain/loss of a hydrogen bond involved in peptide binding. \nIn addition, the application of a short bread challenge allowed for the detection of gluten reactive T cells in peripheral blood of CD patients using flow cytometry and MHC tetramers. This opens for the use of MHC tetramers as a diagnostic tool for diseases where the antigen and MHC restriction elements are known.
Author: Lars‐Egil Fallang
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2470478694