Sollid, Ludvig M., Tye-Din, Jason A., Qiao, Shuo-Wang, Anderson, Robert P., Gianfrani, Carmen, and Koning, Frits
Subjects
HLA histocompatibility antigens, EPITOPES, GLUTEN, GLUTELINS, CELIAC disease, T cells, T cell receptors
Abstract
Celiac disease is caused by an abnormal intestinal T cell response to cereal gluten proteins. The disease has a strong human leukocyte antigen (HLA) association, and CD4+ T cells recognizing gluten epitopes presented by disease-associated HLA-DQ allotypes are considered to be drivers of the disease. This paper provides an update of the currently known HLA-DQ restricted gluten T cell epitopes with their names and sequences. [ABSTRACT FROM AUTHOR]
T cells, GLUTEN, EPITOPES, GLUTELINS, CELIAC disease, CYTOTOXIC T cells, T cell receptors
Abstract
Celiac disease is a chronic inflammatory condition of the small intestine caused by aberrant adaptive immune response to gluten protein from wheat and related cereal plants. Over 90% of celiac disease patients carry the HLA-DQ2.5 allotype and HLA-DQ2.5 presents gluten peptides to gluten-reactive CD4+ T cells in celiac disease patients. A large number of HLA-DQ2.5-restricted gluten T cell epitopes have been identified over the years. These epitopes are in general proline-rich and contain at least one glutamic acid residue that is generated from glutamine in the native gluten protein by deamidation. The deamidation is mediated by the enzyme transglutaminase 2 (TG2). It has been shown that the same T cell could recognize several different HLA-DQ2.5-restricted gluten T cell epitopes due to sequence similarities. In this paper, we demonstrate that three T cell clones derived from duodenal biopsies of different celiac disease patients are able to respond to at least five different gluten T cell epitopes within the DQ2.5-glia-γ4 epitope family, including two novel epitopes. [ABSTRACT FROM AUTHOR]