User:Pdeitiker/TOIG

DQ2.5 restricted T-cell sites and binding

Peptide	Isoform	Native	Deamidated	Binding
or Motif	where found	Seqeunce	Seqeunce	Coefficient
"E~E~E 33mer"	synthetic	(see Text)	E~E~E	0.4 μM
"33mer" + TG2	α-2 gliadin	(see Text)	E~E~E	0.8 μM
αIII motif	α-2 gliadin	PYPQPQLPY	PYPQPELPY	3.5 μM
αI or "α-9"	α-2,8-11 gliadins	PFPQPQLPY	PFPQPELPY	8 μM
αII motif	α-2 gliadin	PQPQLPYPQ	PQPELPYPQ	15 -19 μM
For binding lower numbers mean stronger binding

Gamma-M369999 gliadin contains 8 T-cell recognition sites, and γ-secalin has 2 T-cell sites (80-93), (117-125). Many γ-gliadins contains the "γ-30" motif (see also: "γ-30" gliadin motifs). The gamma-gliadin of wheat is believed to have a structure most conserved relative to ancestral gliadins. Barley, which is the most distantly related cereal to wheat in Triticeae has one similar T-cell site in its glutinous protein, hordein, (56-69) .

• Already mentioned- gliadin resistance to extensive proteolysis, refine by mentioning 25mer and 33mer.
• yes-Increased epithelial permeability allows longer peptides into villi (secondary sources)
• I want this - other gliadin peptides appear to cause this permeability (one primary source)
• maybe - deficiencies in the cells of CD patients are also permissive (not a prolamin issue).
• yes - innate peptide stimulates mononuclear cells[(MNCs)]
• maybe - mention innate stimulates gamma-delta lymphocytes (those increase IELs, thats them)
• yes - MNCs make IL15
• no - IL15 does 6 additional listed things-not here, too much.
• no - IL15 behaves like IL2 or IL12-not here, too much.
• yes - that [IL15] prime[s] immune response for destruction of villi.
• yes - that the [conversion to coeliacs] proceeds with DQ-presented gliadin peptide.

Gluten immunochemistry

• 1 Innate immunity
  • 1.1 Alpha gliadin 31-43
    • 1.1.1 Intraepithileal lymphocytes and IL15
• 1.2 Infiltrating peptides
• 2 HLA Class I restrictions to gliadin
• 3 HLA-DQ recognition of gluten
  • 3.1 HLA-DQ2.5
    • 3.1.1 DQ2.5 and alpha gliadin
    • 3.1.2 Alpha-2 gliadin
    • 3.1.3 DQ2.5 and gamma gliadin
    • 3.1.4 DQ2 and glutelins
  • 3.2 DQ2.2 restricted gliadin sites
  • 3.3 HLA-DQ8
• 4 Antibody recognition

Gluten sensitivity

• 1 Causes of gluten sensitivity
  • 1.1 Gluten toxicity
  • 1.2 Immunochemistry of glutens
• 2 Separating forms of Gluten sensitivity
• 3 Gluten-sensitive enteropathy
• 4 Idiopathic gluten sensitivity
  • 4.1 Neuropathies
  • 4.2 Other conditions
• 5 Gluten-allergy related sensitivities
• 6 Comparative pathophysiology

Prolamins

Illustration of 2 alpha gliadins showing 2 proteolytically resistant sites, Top shows 6 T-cells sites in 33mer, and bottom shows innate immune peptide and two CXCR3 binding sites

The proteins in food responsible for the immune reaction in coeliac disease are the prolamins. These are storage proteins rich in proline (prol-) and glutamine (-amin) that dissolve in alcohols and are resistant to pepsin and chymotrypsin, the two main digestive proteases in the gut. Gliadin in wheat is the best-understood member of this family, but other prolamins exist and hordein (from barley), and secalin (from rye) may contribute to coeliac disease. However, not all prolamins will cause this immune reaction and there is ongoing controversy on the ability of avenin (the prolamin found in oats) to induce this response in coeliac disease. [Bolded statement needs to be moved.]