T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1.

Recent research has implicated a large number of gluten-derived peptides in the pathogenesis of celiac disease, a preponderantly HLA-DQ2-associated disorder. Current evidence indicates that the core of some of those peptides is ten amino acids long, while HLA class II normally accommodates nine amino acids in the binding groove. We have now investigated this in detail, using gluten-specific T-cell clones, HLA-DQ2-specific peptide-binding assays and molecular modelling.

New chelation strategy allows for quick and clean 99mTc-labeling of synthetic peptides.

Analogues of bombesin have been synthesized in which a N2S2 (bis-mercaptoacetyl functionalized diaminopropionic acid) or a N3S (mercaptoacetyl-Gly-Gly-Gly) radiometal-chelating center has been incorporated that allows radiolabeling of these peptides with 99mTc without the need for conjugation or harsh reaction conditions. A mild radiolabeling is possible by using an acetyl-moiety as sulfur protecting group, which can be removed by mild hydroxylamine-treatment at room temperature before radiolabeling. Retained receptor binding is demonstrated in competitive binding experiments with 99mTc-radiolabeled peptides and PC-3 cells with bombesin receptors.

The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses.

In patients with celiac disease, inflammatory T cell responses to HLA-DQ2-bound gluten peptides are thought to cause disease. Two types of HLA-DQ2 molecules exist, termed HLA-DQ2.5 and HLA-DQ2.

Characterization of cereal toxicity for celiac disease patients based on protein homology in grains.

Background And Aims: Celiac disease is caused by T-cell responses to wheat gluten-derived peptides. The presence of such peptides in other widely consumed grains, however, has hardly been studied.

Methods: We have performed homology searches to identify regions with sequence similarity to T-cell stimulatory gluten peptides in the available gluten sequences: the hordeins of barley, secalins of rye, and avenins of oats.