Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls

Abstract

The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.

The Role of Serological Tests in Redefining Coeliac Disease

“…168 HLA DQ2-restricted gliadin-specific T cells have been demonstrated in small intestinal biopsies of CD patients but not from non-CD controls. 169 This finding supports the belief that mucosal T cells recognise gliadin peptides in association with DQ2 molecules. In vitro studies have recently shown that TTG produces a selective deamidation of glutamine residues (from glutamine to glutamate) of pepsin-trypsin digested gliadin creating a protein which is more easily recognised by gut-derived T cells when presented by DQ2 molecules.…”

Occurrence of Nonceliac Gluten Sensitivity in Patients with Allergic Disease

“…The observation that CD is strongly associated with DQ2- or DQ8-encoded heterodimers or with a single molecule implies that CD4+ T cells play a pivotal role in the disease pathogenesis. Indeed, gluten-specific CD4+ T cells can be isolated from intestinal biopsies of CD patients but not from controls [4,5]. The CD4+ cells are TCRαβ+ and typically belong to the Th1 phenotype, secreting large amounts of IFN-γ and TNF-α, in addition to other pro-inflammatory cytokines [6].…”

A Quantitative Analysis of Transglutaminase 2-Mediated Deamidation of Gluten Peptides: Implications for the T-cell Response in Celiac Disease

“…Gluten-specific CD4 + intestinal T cells restricted by DQ2 or DQ8 can be isolated from celiac lesion of CD patients but not of healthy controls. 7,8 Interestingly, these T cells usually recognize gluten peptides that have been post-translationally modified in which a negative charge is introduced by conversion of glutamine to glutamic acid. This deamidation process is mediated in vivo and in vitro by the enzyme transglutaminase 2 (TG2).…”