Peptide analysis, stability studies, and structural modeling explain contradictory peptide motifs and unique properties of the NOD mouse MHC class II molecule H2-A(g7)
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Ημερομηνία
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Περιοδικό ISSN
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Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
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Όνομα περιοδικού
Eur J Immunol
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Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The MHC class II molecule H2-A(g7) is the chief genetic determinant in insulin-dependent diabetes mellitus of the non-obese diabetic (NOD) mice. Poor peptide binding ability, as well as presentation of a unique subset of peptides by this molecule was suggested to promote autoimmunity in this strain. However, several laboratories have presented results in favor of an H2-A(g7) molecule that can avidly bind many different peptides. The crystal structures of H2-A(g7) in complex with two different peptides did not completely resolve this issue. To analyze the peptide binding capacity and the motif requirements of H2-A(g7), we eluted natural ligands from purified H2-A(g7) molecules isolated from the H2-A(g7)-transfected M12-C3 cells. A low peptide yield dominated by a few peptide ligands was found. Pool sequencing and alignment of individual ligands on the basis of molecular modeling revealed a peptide-binding motif with basic/aliphatic/small hydrophilic amino acids at relative position 1 (p1), aliphatic amino acids at p4, Ala at p6, and acidic amino acids and Ser/Gly at p9, as well as acidic residues at p10/11. Though weak, the binding of individual ligands, as well as the importance of an acidic C-terminal residue was confirmed by peptide binding studies to isolated H2-A(g7) molecules. Furthermore, the H2-A(g7) molecule incompletely dissociated into its constituent chains in SDS-electrophoresis under nonreducing conditions. This provides additional evidence of its weak affinity for peptides, which probably arises from the combination of beta56His/beta57Ser/beta78Ala and other unique H2-A(g7) residues in contact with the antigenic peptide. These results allow a better understanding of the role of this molecule in the development of autoimmunity and the identification of epitopes relevant to diabetes.
Περιγραφή
Λέξεις-κλειδιά
Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Line, Diabetes Mellitus, Type 1/genetics/*immunology, Histocompatibility Antigens Class II/analysis/*chemistry, Mice, Mice, Inbred NOD, Models, Structural, Molecular Sequence Data
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Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/12209622
http://onlinelibrary.wiley.com/store/10.1002/1521-4141(200208)32:8<2105::AID-IMMU2105>3.0.CO;2-Q/asset/2105_ftp.pdf?v=1&t=h0ustzd0&s=7a6c29c79d6fe9373d459190278fbbf9a64d24ff
http://onlinelibrary.wiley.com/store/10.1002/1521-4141(200208)32:8<2105::AID-IMMU2105>3.0.CO;2-Q/asset/2105_ftp.pdf?v=1&t=h0ustzd0&s=7a6c29c79d6fe9373d459190278fbbf9a64d24ff
Γλώσσα
en
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Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής