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Immunodominant Peptide Identified in Celiac Disease

Nat Med 2000;6:337-342. (March 1, 2000)
see also: BMJ 2000;320:736 (March 18, 2000)

(Celiac.com 03/17/2000) Researchers in Britain have identified a dominant epitope of the A-gliadin protein of wheat that is linked to the cause of celiac disease. The findings could eventually influence the diagnosis and treatment of the disease. With the new information Wheat could be genetically engineered to be non-toxic for celiacs, according to Dr. Robert P. Anderson. Also, modified versions of T cell epitopes can have unique antagonistic effects that switch off particular immune responses. The identification of this peptide could be used to develop a blood tests to better diagnose celiac disease, and could also be used to better test food for celiac toxicity.

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Dr. Anderson and his University of Oxford colleagues used a series of 15 amino acid peptides along the A-gliadin sequence (alpha gluten) to stimulate in patients with celiac disease their peripheral blood mononuclear cells, or PBMCs. The peptides were either unmodified or were treated with tissue transglutaminase, which, in the presence or absence of lysine, will convert glutamine to glutamate.

Researchers successfully stimulated PBMCs in celiac patients who were in remission due to a gluten-free diet with a gluten challenge. Patients were fed wheat bread for either a half day, 3 days, or 10 days, and healthy, non-celiac patients that were fed wheat bread each day for 4 weeks were used as controls. The researchers successfully produced PBMCs from the celiac disease group, who secreted interferon-gamma 6-8 days later, in response to a particular pool of A-gliadin peptides, which had been treated with tissue transglutaminase. A 17-amino-acid peptide, corresponding to the partially deamidated peptide of A-gliadin amino acids 57-73, was optimal for inducing the interferon-gamma secretion, and the responses were restricted to those with HLA-DQ2.

According to Dr. Anderson: On a more general level, the finding that a host enzyme modifies peptides that are then recognized by the immune system suggests that searching for epitopes important in disease may be more complex than simply reading off protein sequences from sequenced genes. Further, modification of the peptide by tissue transglutaminase that is present in the intestinal lining increases binding of the peptide to HLA-DQ. The researchers also point out that T cells that are responsive to the same A-gliadin peptide are readily induced in celiac disease despite many years of following a gluten-free diet, which indicates a persistence of memory T cells that could be caused by continuing exposure to trace amounts of gluten. The researchers only looked at the A-gliadin peptide, and point out that there is a possibility that other peptides that are structurally unrelated to A-gliadin are also important in celiac disease.

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Ironic, We went entirely gluten-free in our home after 2016 for how bad my neurological , joints, mood gets now in addition to my former gi, skin, and other issues . My son shows signs of my early symptoms and voluntarily went off gluten, corn, and milk like me as he did his own food like di...

Funny though, my brother and I were just discussing this. He has celiac and both his son and him are gene positive. Both were TTG/EMA negative but never tested for DGP. My brother had damage on endoscopy. They have not scoped his son. He feels his son is symptomatic but not his daughter. I ...

It might generate based on traffic searches or posts etc. My guess. I read them and respond because I wasn't on here as a member in 2012. I only use to visit then. So it's new to me V. happy friday ?

Just saying her TTg was 0 & her IgA was 27 doesn't tell us anything. Every lab can have different values so we need the reference ranges not just the results. Can you look back at the lab report & get those & post them please? Did they tell you she MUST be eating gluten every single day unti...

When the doc did the endoscopy, did he take biopsies? How many? From what locations? Get your records!!!! If he didn't take biopsies for celiac disease then he can NOT say you don't have it. 99% of the time, villi damage can not be SEEN by the GI doc during the endoscopy. And yes, the doc has no ...