Abstract
Gluten fragments released in gut of celiac individuals activate the innate or adaptive immune systems. The molecular mechanisms associated with the adaptive response involve a series of immunodominant gluten peptides which are mainly recognized by human leucocyte antigen (HLA)-DQ2.5 and HLA-DQ8. Other peptides, such as A-gliadin P31–43, are not recognized by HLA and trigger innate responses by several routes not yet well detailed. Among the gluten fragments known to be active in Celiac disease, here we focus on the properties of all gluten peptides with known tri-dimensional structure either those locked into HLA-DQ complexes whose crystals were X-ray analyzed or characterized in solution as free forms. The aim of this work was to find the structural reasons why some gluten peptides prompt the adaptive immune systems while others do not, by apparently involving just the innate immune routes. We propose that P31–43 is a non-adaptive prompter because it is not a good ligand for HLA-DQ. Even sharing a similar ability to adopt polyproline II structure with the adaptive ones, the way in which the proline residues are located along the sequence disfavors a productive P31–43-HLA-DQ binding.
Highlights
The peptides deriving from the digestion of gluten proteins of wheat, barley, oats, and rye cause immune reactions and inflammation of the intestinal mucosa
Previous research about the chain of pathological events related to Celiac disease (CeD) led to the identification of human leucocyte antigen (HLA) as the molecular player deputed to present the antigenic peptides to T-cells [1]
We report our analysis of all the known X-ray binary and ternary complexes involving gluten fragments in HLA-DQ and HLA/T-cells antigen receptor (TCR) complexes with the aim to catch, if any, the structural properties that make specific gluten fragments immune-dominant epitopes and some others, like gliadin P31–43, non-ligands
Summary
The peptides deriving from the digestion of gluten proteins of wheat, barley, oats, and rye cause immune reactions and inflammation of the intestinal mucosa. The enzymatic hydrolysis of the hundred proteins contained in the gluten causes the release of peptides in the gut, some of which are able to activate the innate or adaptive immune systems. The molecular mechanism associated to the innate immune response to gluten peptides is less detailed than that associated to the adaptive response. Previous research about the chain of pathological events related to Celiac disease (CeD) led to the identification of human leucocyte antigen (HLA) as the molecular player deputed to present the antigenic peptides to T-cells [1].
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