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

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..