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Design of new high-affinity peptide ligands for human leukocyte antigen-DQ2 using a positional scanning peptide library.


Human leukocyte antigen (HLA)-DQ2 (DQA1 x 0501/DQB1 x 0201) is associated with several immune disorders, including celiac disease, which is caused by an inappropriate T-cell response to gluten. Interference with peptide presentation by HLA-DQ2, for example, by the use of peptide blockers, is a possible treatment strategy for such HLA-associated disorders. A successful implementation of this strategy will depend on the identification of ligands that bind much better to HLA-DQ2 than the disease related epitopes. We have used a positional scanning nonapeptide library to determine the optimal amino acids for each position of the HLA-DQ2 binding frame. By combining the optimal residues in each position, we were able to design high affinity binders to HLA-DQ2. Interestingly, the decapeptide with highest affinity was composed of the most favorable residues in each position. This sequence bound 50-fold better than the immunodominant gluten epitope DQ2-alpha-I-gliadin, which makes it an interesting lead compound for the development of blockers. For some natural HLA-DQ2 ligands, the correlation between measured and predicted affinities was poorer, but notably these peptides did not have optimal amino acids at all positions. Our approach represents a straightforward strategy for developing high-affinity binders to HLA class II molecules.


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    Centre for Immune Regulation, Institute of Immunology, Oslo University Hospital-Rikshospitalet, 0027 Oslo, Norway.

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    Human immunology 71:5 2010 May pg 475-81


    Amino Acid Sequence
    HLA-DQ Antigens
    Molecular Sequence Data
    Peptide Library
    Protein Binding
    Spectrometry, Mass, Electrospray Ionization

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't



    PubMed ID