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Celiac Disease Association with CD8⁺ T Cell Responses: Identification of a Novel Gliadin-Derived HLA-A2-Restricted Epitope¹

Carmen Gianfrani^2,*, Riccardo Troncone^*,, Patrizia Mugione, Elena Cosentini, Mariateresa De Pascale, Clementina Faruolo^*, Stefania Senger^*, Giuseppe Terrazzano, Scott Southwood^¶, Salvatore Auricchio and Alessandro Sette^||

^* Institute of Food Science and Technology, Consiglio Nazionale delle Ricerche, Avellino, Italy; Departments of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases and Molecular and Cellular Biology and Pathology, and Immunohematology and Transfusion Medicine, University Federico II, Naples, Italy; ^¶ Epimmune, and ^|| La Jolla Institute for Allergy and Immunology, San Diego, CA 92121

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- 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 -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.

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