Celiac disease association with CD8+ T cell responses: identification of a novel gliadin-derived HLA-A2-restricted epitope.
One of the diagnostic hallmarks of the histological lesions associated with celiac disease is the extensive infiltration of the small intestinal epithelium by CD8(+) T cells of unknown Ag specificity. In this study, we report recognition of the gliadin-derived peptide (A-gliadin 123-132) by CD8(+) T lymphocytes from celiac patients. A-gliadin 123-132-specific IFN-gamma production and cytotoxic activity were detected in PBMCs derived from patients on gluten-free diet, but not from either celiac patients on gluten-containing diet or healthy controls. In contrast, A-gliadin 123-132-specific cells were isolated from small intestine biopsies of patients on either gluten-free or gluten-containing diets. Short-term T cell lines derived from the small intestinal mucosa and specific for the 123-132 epitope recognized human APC pulsed with either whole recombinant alpha-gliadin or a partial pepsin-trypsin gliadin digest. Finally, we speculate on a possible mechanism leading to processing and presentation of class I-restricted gliadin-derived epitopes in celiac disease patients.
Gianfrani
Carmen
C
Institute of Food Science and Technology, Consiglio Nazionale delle Ricerche, Avellino, Italy. cgianfrani@isa.av.cnr.it
Troncone
Riccardo
R
Mugione
Patrizia
P
Cosentini
Elena
E
De Pascale
Mariateresa
M
Faruolo
Clementina
C
Senger
Stefania
S
Terrazzano
Giuseppe
G
Southwood
Scott
S
Auricchio
Salvatore
S
Sette
Alessandro
A
D000293:Adolescent; D000328:Adult; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology*; D005903:Gliadin / Q000097:blood / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000097:blood / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood / Q000276:immunology; D011499:Protein Processing, Post-Translational / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D005903:Gliadin