Editing Coeliac disease (section)

===Prolamins===
The majority of the proteins in food responsible for the immune reaction in coeliac disease are the [[prolamin]]s. These are storage proteins rich in [[proline]] (''prol-'') and [[glutamine]] (''-amin'') that dissolve in alcohols and are resistant to [[protease]]s and [[peptidase]]s of the gut.<ref name=VanHeelWest/><ref name="pmid17960014">{{cite journal |vauthors=Green PH, Cellier C |title=Celiac disease |journal=N. Engl. J. Med. |volume=357 |issue=17 |pages=1731–43 |year=2007 |pmid=17960014 |doi=10.1056/NEJMra071600}}</ref> Prolamins are found in cereal grains with different grains having different but related prolamins: wheat (gliadin), barley ([[hordein]]), rye ([[secalin]]) and [[oat]]s ([[avenin]]).<ref name=Biesiekierski2017 /> One region of [[Gliadin|α-gliadin]] stimulates membrane cells, [[enterocyte]]s, of the intestine to allow larger molecules around the sealant between cells. Disruption of [[tight junctions]] allow peptides larger than three [[amino acid]]s to enter the intestinal lining.<ref name="pmid18485912">{{cite journal |vauthors=Lammers KM, Lu R, Brownley J, Lu B, Gerard C, Thomas K, Rallabhandi P, Shea-Donohue T, Tamiz A, Alkan S, Netzel-Arnett S, Antalis T, Vogel SN, Fasano A |title=Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3 |journal=Gastroenterology |volume=135 |issue=1 |pages=194–204.e3 |year=2008 |pmid=18485912 |pmc=2653457 |doi=10.1053/j.gastro.2008.03.023}}</ref>

[[File:A2-gliadin-33mer.png|thumb|upright=1.2|Illustration of deamidated α-2 gliadin's 33mer, amino acids 56–88, showing the overlapping of three varieties of T-cell epitope<ref name="pmid15265905">{{cite journal | vauthors = Qiao SW, Bergseng E, Molberg Ø, Xia J, Fleckenstein B, Khosla C, Sollid LM | title = Antigen presentation to celiac lesion-derived T cells of a 33-mer gliadin peptide naturally formed by gastrointestinal digestion | journal = Journal of Immunology | volume = 173 | issue = 3 | pages = 1757–1762 | date = August 2004 | pmid = 15265905 | doi = 10.4049/jimmunol.173.3.1757 | doi-access = free }}</ref>]]
Membrane leaking permits peptides of gliadin that stimulate two levels of the immune response: the innate response, and the adaptive (T-helper cell-mediated) response. One protease-resistant peptide from α-gliadin contains a region that stimulates lymphocytes and results in the release of [[interleukin-15]]. This [[Gluten immunochemistry#Innate immunity|innate response to gliadin]] results in immune-system signalling that attracts inflammatory cells and increases the release of inflammatory chemicals.<ref name=VanHeelWest/> The strongest and most common adaptive response to gliadin is directed toward an [[Gluten immunochemistry#A2-gliadin|α2-gliadin fragment]] of 33&nbsp;amino acids in length.<ref name=VanHeelWest/>

The response to the 33mer occurs in most coeliacs who have [[HLA-DQ2#DQ2.5 and gluten|a DQ2]] [[wikt:isoform|isoform]]. This peptide, when altered by intestinal transglutaminase, has a high density of overlapping T-cell epitopes. This increases the likelihood that the DQ2 isoform will bind, and stay bound to, peptide when recognised by T-cells.<ref name="pmid15265905"/> Gliadin in wheat is the best-understood member of this family, but other prolamins exist, and hordein (from barley), secalin (from rye), and avenin (from oats) may contribute to coeliac disease.<ref name=VanHeelWest/><ref name=Biesiekierski2017 /><ref name="pmid16212427">{{cite journal |vauthors=Shan L, Qiao SW, Arentz-Hansen H, Molberg Ø, Gray GM, Sollid LM, Khosla C |title=Identification and analysis of multivalent proteolytically resistant peptides from gluten: implications for celiac sprue |journal=J. Proteome Res. |volume=4 |issue=5 |pages=1732–41 |year=2005 |pmid=16212427 |pmc=1343496 |doi=10.1021/pr050173t}}</ref> Avenin's toxicity in people with coeliac disease depends on the oat [[cultivar]] consumed, as prolamin genes, protein amino acid sequences, and the immunoreactivities of toxic prolamins vary among oat varieties.<ref name=CominoMoreno2015 />