Selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity.
Celiac disease (CD) is caused by gluten ingestion in susceptible individuals. Tissue transglutaminase (tTG)-specific Abs are characteristic of CD, and increased tTG activity has been observed in the jejunal biopsies of patients. Here we demonstrate that tTG selectively deamidates gluten peptides, which results in strongly enhanced T cell-stimulatory activity. To our knowledge, this is the first example of an enzymatic modification of a food protein that affects T cell recognition. Moreover, these modifications may lead to the amplification of gluten-specific T cell responses in the gut and consequently may be important for the development of CD.
van de Wal
Y
Y
Department of Immunohaematology and Bloodbank, Leiden University Medical Center, The Netherlands. wal@rullf2.leidenuniv.nl
Kooy
Y
Y
van Veelen
P
P
Peña
S
S
Mearin
L
L
Papadopoulos
G
G
Koning
F
F
D000577:Amides / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005903:Gliadin / Q000276:immunology* / Q000494:pharmacology; D018698:Glutamic Acid / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology*; D011503:Transglutaminases / Q000378:metabolism* / Q000494:pharmacology
D000577:Amides; D000939:Epitopes; D010446:Peptide Fragments; D005973:Glutamine; C052013:gliadin peptide A (206-217); D018698:Glutamic Acid; D005903:Gliadin; D011503:Transglutaminases