SEVERAL COMMON HLA-DR TYPES SHARE LARGELY OVERLAPPING PEPTIDE BINDINGREPERTOIRES

The peptide binding specificities of HLA-DRB10401, DRB1*0101, and DRB 10701 have been analyzed by the use of large collections of synthetic peptides corresponding to naturally occurring sequences. The results demonstrated that nearly all peptides binding to these DR molecules be ar a motif characterized by a large aromatic or hydrophobic residue in position 1 (Y, F, W, L, I, V, M) and a small, noncharged residue in p osition 6 (S, T, C, A, P, V, I, L, M). In addition, allele-specific se condary effects and secondary anchors were defined, and these paramete rs were utilized to derive allele-specific motifs and algorithms. By t he combined use of such algorithms, peptides capable of degenerate DRB 10101, DRB1*0401, and DRB1*0701 binding were identified. Additional e xperiments utilizing a panel of quantitative assays specific for nine additional common DR molecules identified a large set of DR molecules, which includes at least the DRB10101, DRB1*0401, DRB1*0701, DRB5*010 1, DRB11501, DRB1*0901, and DRB1*1302 allelic products, characterized by overlapping peptide-binding repertoires. These results have implic ations for understanding the molecular interactions involved in peptid e-DR binding, as well as the genetic and structural basis of MHC polym orphism. These results also have potential practical implications for the development of epitope-based prophylactic and therapeutic vaccines .