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. 2001 Nov;108(9):1261-6.
doi: 10.1172/JCI14344.

Interplay between genetics and the environment in the development of celiac disease: perspectives for a healthy life

G K Papadopoulos  1 , C Wijmenga, F Koning
Affiliations

Interplay between genetics and the environment in the development of celiac disease: perspectives for a healthy life

G K Papadopoulos et al. J Clin Invest. 2001 Nov.
No abstract available

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Figures

Figure 1
Figure 1
T cell receptor view of the α1β1 domain of the modeled structure of the HLA-DQA1*0501/B1*0201 (DQ2) complexed with the α-I gliadin peptide, one of the dominant epitopes in adult DQ2-restricted CD. The protein molecule is in solid surface representation with colors according to the surface electrostatic potential (gray, neutral; blue, positive; red, negative). The antigenic peptide residues are in van der Waals space filling form, while the few DQ residues shown are in stick representation (color convention: red, oxygen; blue, nitrogen; green, carbon; white, hydrogen). Anchor residues at p1 and p9 point into the plane of the paper and are thus not visible. Secondary structure elements of the DQ2 are also shown for orientation purposes: α-helix in red, β-pleated sheet in turquoise, and random coil in gray. A transparency function has been included so that the secondary structural elements of DQ2 and the peptide residues buried by DQ2 residues become slightly visible. DQ2 is unique among MHC II alleles as it contains β70Arg/β71Lys, a combination responsible for the preference of acidic residues at p4/p7. Also, positions β28 and β30 are occupied by serine residues and β37 by isoleucine (instead of Tyr for nearly all other DQB alleles), thus allowing ample space at p9 for the bulky and inflexible aromatic residues (here Tyr), the only DQ allele documented with this binding property to date. In this peptide, residue p6 has been transformed by tTG from Gln to Glu, making the peptide a better binder of DQ2 (3, 9, 39). Homology modeling, based on the coordinates of DQ8-insulin B9-23 complex, kindly provided by Kon Ho Lee (40), was performed via the program Discover II (MSI, San Diego, California, USA) and depiction on WebLabViewer 3.5 (MSI).
Figure 2
Figure 2
T cell receptor view of the α1β1 domain of DQA1*0301/B1*0302 (DQ8) complexed with the α-I gliadin peptide, identified as a DQ8-specific epitope (Table 1). Color conventions and representations are as in Figure 1. DQ8 is also unique in its preference for acidic residues at p1 and p9 (40−43). These anchors also point into the plane of the paper and are not visible to the viewer. Four arginines around p1 (α49, α50, α52 [not shown], and α53) are responsible for the preference of an acidic residue at p1, and α76Arg is responsible for a similar preference at p9. The peptide shown here is the transformed gliadin peptide (p1/9Glu), which is recognized by the same T cell clone, but at a higher sensitivity than the native one (p1/9Gln) (1, 6, 9, 43).
See this image and copyright information in PMC

References

    1. Wal Y, et al. Small intestinal cells of celiac disease patients recognize a natural pepsin fragment of gliadin. Proc Natl Acad Sci USA. 1988;95:10050–10055. - PMC - PubMed
    1. Wal Y, et al. Glutenin is involved in the gluten-driven mucosal T cell response. Eur J Immunol. 1999;29:3133–3139. - PubMed
    1. Sjöström H, et al. Identification of a gliadin epitope in coeliac disease: general importance of gliadin deamidation for intestinal T cell recognition. Scand. J Immunol. 1998;48:111–115. - PubMed
    1. Arentz-Hansen H, et al. The intestinal T cell response to α-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med. 2000;191:603–612. - PMC - PubMed
    1. Anderson RP, Degano P, Godkin AJ, Jewell DP, Hill A. In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope. Nat Med. 2000;6:337–342. - PubMed

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