The motif for peptide binding to the insulin-dependent diabetes mellitus-associated class II MHC molecule I-A(g7) validated lay phage display library

Silvia Gregori, Elisa Bono, Fabio Gallazzi, Juergen Hammer, Leonard C. Harrison, Luciano Adorini

Research output: Contribution to journalArticlepeer-review

Abstract

The MHC class II molecule I-A(g7) is essential for the development of insulin-dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse but the requirements for peptide binding to I-A(g7) are still controversial. We have now isolated I-A(g7)-binding phage from a large phage display library encoding random nonamer peptides. Ninety peptide-encoding regions of phage eluted from I-A(g7) were sequenced and > 75% of the corresponding synthetic peptides bound to I-A(g7). Peptide alignment led to the identification of position-specific anchor residues. Hydrophobic (V and P) and positively charged (K) residues were highly enriched at P6 and positively charged (R and K), aromatic (Y) or hydrophobic (L) residues at P9. In addition, small amino acid residues (G and A) were enriched at P7 and G at P8. The primary anchors at P6 and P9 defining the phage-derived motif were present in most high-affinity I-A(g7)-binding peptides from IDDM candidate antigens but only in ≤ 25% of peptides that were low-affinity binders or failed to bind to I-A(g7). A comparison of these results with the proposed motifs for peptide binding to I-A(g7) validates the one we have previously described.

Original languageEnglish
Pages (from-to)493-503
Number of pages11
JournalInternational Immunology
Volume12
Issue number4
Publication statusPublished - 2000

Keywords

  • I-A(g7)
  • Insulin-dependent diabetes mellitus
  • Non-obese diabetic mice
  • Peptide-binding motif

ASJC Scopus subject areas

  • Immunology

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