@Maurader - or whomever
They are saying that in people with Celiac Disease the gluten, or more correctly gliadin peptides (antigen) being presented to the T-cells in people with Celiac Disease are actually structurally different. Because of this structural difference, the gliadin peptides now bind stronger to HLA molecules in people with HLA-DQ2 and HLA-DQ8 alleles which makes the Gliadin more antigenic to them.
So now they are adding to the above, this: That Transglutaminase 2 (an enzyme) is what is actually responsible for this this structural alteration in the gliadin peptide which increases binding affinity in people with these HLA alleles (HLA-DQ2 or HLA-DQ8).
They are also saying that in people with “true Celiac Disease”, they also have B-cells that produce antibodies to Tranglutaminase 2 which is “auto-reacitve”. More so this ONLY takes place when the enzyme (Tranglutaminase 2) is in its active form. So only when there are cellular processes going on internally that cause Transglutamine 2 to be in its active form or
Together these cause two things:
1) T-cells in people with “true Celiac Disease” mount a stronger response the structurally altered (and more antigenic) gladin peptide.
2) The T-cells (CD4+ or helper T-cells) responding to the structurally altered and higher affinity gliadin antigen in turn, (through a bunch of processes) then end up stimulating these Transglutamine 2 reactive B-cells to produce antibodies to Transglutamine 2 when it’s in active form (
open conformation) and this now triggers a strong immune response that is directed at self-tissues.
Take away the gluten (or gliadin peptieds) and this reaction stops.
This, I believe is what they are proposing is the cause of “True Celiac Disease” in those with HLA-DQ2 or HLA-DQ8 alleles.
So there are a lot of b-cells in the gut… about
20 Billion. So when this reaction takes place the effect could be pretty darn intense.
I think are also saying or questioning if something similar can take place where a reaction like this can occur perhaps to some other “foreign” peptide (so maybe not gliadin but something else) from a bacteria or virus etc and as long as that peptide is present in our bodies and as long as we have some genetic predisposition like a certain HLA allele, some sort of auto-reactive immune response could occur similar to the above.
Post Edited (Canada Mark) : 6/30/2015 5:03:59 PM (GMT-6)