Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin.
Celiac disease is a common severe intestinal disease resulting from intolerance to dietary wheat gluten and related proteins. The large majority of patients expresses the HLA-DQ2 and/or DQ8 molecules, and gluten-specific HLA-DQ-restricted T cells have been found at the site of the lesion in the gut. The nature of peptides that are recognized by such T cells, however, has been unclear so far. We now report the identification of a gliadin-derived epitope that dominantly is recognized by intestinal gluten-specific HLA-DQ8-restricted T cells. The characterization of such epitopes is a key step toward the development of strategies to interfere in mechanisms involved in the pathogenesis of celiac disease.
van de Wal
Y
Y
Department of Immunohaematology and Bloodbank, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. wal@rullf2.leidenuniv.nl
Kooy
Y M
YM
van Veelen
P A
PA
Peña
S A
SA
Mearin
L M
LM
Molberg
O
O
Lundin
K E
KE
Sollid
L M
LM
Mutis
T
T
Benckhuijsen
W E
WE
Drijfhout
J W
JW
Koning
F
F
D000595:Amino Acid Sequence; D002446:Celiac Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells; D005903:Gliadin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006683:HLA-DQ Antigens; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010434:Pepsin A; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D005903:Gliadin; D010434:Pepsin A