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    Different Binding Motifs of the Celiac-associated HLA Molecules DQ2.5, DQ2.2, and DQ7.5


    Jefferson Adams

    Celiac.com 02/18/2015 - It's well documented that HLA-DQ molecules play a role in the pathogenesis of celiac disease through the presentation of gluten peptides to CD4(+) T cells. The α- or β-chain sharing HLA molecules DQ2.5, DQ2.2, and DQ7.5 display different risks for the disease.

    Photo: CC--Thierry EhrmannResearchers have recently showed that T cells of DQ2.5 and DQ2.2 patients recognize distinct sets of gluten epitopes, which indicates that these two DQ2 variants select different peptides for display.

    To figure out if this is the case, the research team performed a comprehensive comparison of the endogenous self-peptides bound to HLA-DQ molecules of B-lymphoblastoid cell lines. The research team included E. Bergseng, S. Dørum, M. Arntzen, M. Nielsen, S. Nygård, S. Buus, G.A. de Souza, and L.M. Sollid. They are variously affiliated with the Centre for Immune Regulation, Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.

    The team began by isolating peptides from affinity-purified HLA molecules of nine cell lines. They then subjected the isolated peptides to quadrupole orbitrap mass spectrometry and MaxQuant software analysis. They identified 12,712 endogenous peptides at very different relative abundances. Hierarchical clustering of normalized quantitative data revealed significant differences in repertoires of peptides between the three DQ variant molecules.

    They identified peptide-binding motifs using the neural network-based method, NNAlign. The binding motifs of DQ2.5 and DQ7.5 concurred with previously established binding motifs, but the binding motif of DQ2.2 was remarkably different from that of DQ2.5, with position, P3 being a major anchor having a preference for threonine and serine.

    This is interesting for the reason that three recently identified epitopes of gluten recognized by T cells of DQ2.2 celiac patients harbor serine at position P3.

    This study shows that relative quantitative comparison of endogenous peptides sampled from our protein metabolism by HLA molecules can provide clues to understand HLA association with disease.

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, and science. He previously served as Health News Examiner for Examiner.com, and provided health and medical content for Sharecare.com.

    Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book Dangerous Grains by James Braly, MD and Ron Hoggan, MA.

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