“…First, since there is genetic variability between c~-gliadins (16)(17)(18), these findings do not allow us to definitively exclude that the T cells actually recognize peptides from this region. Second, although diseaserelevant epitopes can be found in the NH2-terminal region of ol-gliadin (39,40), other regions in both cx-gliadin (39,41) and other gliadins have been suggested to be implicated in the disease (38,(42)(43)(44).…”
SummaryCeliac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the c/s or trans encoded HLA-DQ(o~I*O5OI,fll*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25 + T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen-presenting molecule was established to be the CD-associated DQ(oel*0501, fl1"0201) heterodimer. The gluten-reactive T cell clones were CD4 +, CD8-, and carried diverse combinations of T cell receptor (TCR) Vc~ and Vfl chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(c~I*OSO1,BI*0201) in CD, which may explain the HLA association.
“…First, since there is genetic variability between c~-gliadins (16)(17)(18), these findings do not allow us to definitively exclude that the T cells actually recognize peptides from this region. Second, although diseaserelevant epitopes can be found in the NH2-terminal region of ol-gliadin (39,40), other regions in both cx-gliadin (39,41) and other gliadins have been suggested to be implicated in the disease (38,(42)(43)(44).…”
SummaryCeliac disease (CD) is most probably an immunological disease, precipitated in susceptible individuals by ingestion of wheat gliadin and related proteins from other cereals. The disease shows a strong human HLA association predominantly to the c/s or trans encoded HLA-DQ(o~I*O5OI,fll*0201) (DQ2) heterodimer. T cell recognition of gliadin presented by this DQ heterodimer may thus be of immunopathogenic importance in CD. We therefore challenged small intestinal biopsies from adult CD patients on a gluten-free diet in vitro with gluten (containing both gliadin and other wheat proteins), and isolated activated CD25 + T cells. Polyclonal T cell lines and a panel of T cell clones recognizing gluten were established. They recognized the gliadin moiety of gluten, but not proteins from other cereals. Inhibition studies with anti-HLA antibodies demonstrated predominant antigen presentation by HLA-DQ molecules. The main antigen-presenting molecule was established to be the CD-associated DQ(oel*0501, fl1"0201) heterodimer. The gluten-reactive T cell clones were CD4 +, CD8-, and carried diverse combinations of T cell receptor (TCR) Vc~ and Vfl chains. The findings suggest preferential mucosal presentation of gluten-derived peptides by HLA-DQ(c~I*OSO1,BI*0201) in CD, which may explain the HLA association.
“…Likewise, human AGA can in principle cross‐react either with large molecules containing both specific linear or β‐turn motifs, or with peptides showing a low degree of sequence identity, provided they are rich in β‐turn moiety. This could explain why all coeliac sera react with gliadins, hordeins [18–20], secalins [21]and avenins [22]regardless whether the coeliac patient has consumed wheat, barley, rye or oats in the diet.…”
A 20-amino acid synthetic peptide from the Nterminal region of Q Q3 avenin yields a surprisingly strong reactivity with anti-gliadin antibodies (AGA) of coeliac sera, comparable to that of a gliadin extract. In contrast, a low reactivity is observed with five similar peptides derived from K Kgliadin, Q Q70 and g g1 secalins. Circular dichroism studies of these peptides show that the avenin peptide displays the highest L L-turn content (30%), while other peptides yield much lower values. In agreement with circular dichroism data, nuclear magnetic resonance data point to the presence of a L L-turn in the avenin peptide DPSEQ segment, a sequence with a high statistical L Lturn preference. A strong linear dependence between AGA reactivity and L L-turn content was observed for these peptides, indicating for the first time a role of L L-turn motifs in anti-gliadin antibodies recognition in coeliac disease. This suggests that circulating AGA in coeliac patients comprise not only linear but also conformational antibodies against L L-turn motifs. Polyclonal antibodies raised against the avenin peptide containing L L-turn motifs react by immunoblotting with all gliadin, hordein and secalin proteins, which are rich in L L-turn conformations, despite that their primary structures are unrelated to that of the peptide.z 1998 Federation of European Biochemical Societies.
“…Notwithstanding difficulties in methods, controversy exists regarding the value of the specific class of AGA antibodies in the diagnosis of celiac disease. Some investigators advocate IgG class AGA(14‐17); whereas others favor IgA class AGA (18,19), and still others favored both(16,17,20). The usefulness of gliadin antibodies for diagnosis is open for criticism because their sensitivity and specificity varies so much from study to study(21‐26).…”
Section: Serologic Markers For Celiac Diseasementioning
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