ANALYSIS OF PEPTIDE-BINDING MOTIFS FOR 2 DISEASE-ASSOCIATED HLA-DR13 ALLELES USING AN M13 PHAGE DISPLAY LIBRARY

Major histocompatibility complex (MHC) molecules bind peptides bearing an appropriate 'sequence motif for MHC binding. The use of phage disp lay libraries exploits the ability of MHC class II molecules to exchan ge peptides in solution and thus select out peptide sequences with hig h-affinity binding from a large array of random peptides. We have anal ysed the peptide binding motifs of HLA-DRB11301 and *1302 using affin ity purified HLA-DR13 molecules to purify sequentially HLA-DR13-bindin g peptides from a large random library of M13 phage containing nonamer inserts in the pIII coat protein. These DR13 alleles differ only at p osition 86 of the HLA-DR beta chain, where they contain valine and gly cine residues respectively. These alleles were chosen because of their association with protection from severe malaria and chronic hepatitis B virus infection in West Africa. Analysis of the phage bound to thes e DR molecules suggests binding motifs. We compare the results derived from the use of the phage display library with results obtained from analysis of eluted peptides and peptide-binding studies. This analysis shows that although there is a common theme to motifs derived using d ifferent methods, there are also subtle variations between them.