NDLI: Unique peptide binding characteristics of the disease-associated DQ(α1*0501, β1*0201) vs the non-disease-associated DQ(α1*0201, β1*0202) molecule

Content Provider	Springer Nature Link
Author	van de Wal, Y. Kooy, Yvonne M. C. Drijfhout, Jan Wouter Amons, Reiut Papadopoulos, George K. Koning, Frits
Copyright Year	1997
Abstract	To understand the dominant association of celiac disease (CD) with the presence of HLA-DQ(α10501, β10201), the peptide binding characteristics of this molecule were compared with that of the structurally similar, but non-CD-associated DQ(α10201, β10202) molecule. First, naturally processed peptides were acid-extracted from immuno-affinity-purified DQ molecules of both types. Both molecules contained the Ii-derived CLIP sequence and a particular fragment of the major histocompatibility complex (MHC) class I α chain. Use of truncated analogues of these two peptides in cell-free peptide binding assays indicated that identical peptide frames are used for binding to the two DQ2 molecules. Detailed substitution analysis of the MHC class I peptide revealed identical side chain requirements for the anchor residues at p6 and p7. At p1, p4, and p9, however, polar substitutions (such as N, Q, G, S, and T) were less well tolerated in the case of the DQ(α10201, β10202) molecule. The most striking difference between the two DQ molecules is the presence of an additional anchor residue at p3 for the DQ(α10201, β10202) molecule, whereas this residue was found not to be specifically involved in binding of peptides to DQ(α10501, β10201). Similar results were obtained applying substitution analysis of the CLIP sequence. Molecular modelling of the DQ2 proteins complexed with the MHC class I and CLIP peptide corresponds well with the binding data. The results suggest that both CLIP and the MHC class I peptide bind DQ(α10501, β10201) and DQ(α10201, β10202) in a DR-like fashion, following highly similar binding criteria. This detailed characterization of unique peptide binding properties of the CD-associated DQ(α10501, β10201) molecule should be helpful in the identification of CD-inducing epitopes.
Starting Page	484
Ending Page	492
Page Count	9
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	46
Issue Number	6
e-ISSN	14321211
Language	English
Publisher	Springer-Verlag
Publisher Date	1997-10-07
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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