DEVELOPMENT OF HIGH POTENCY UNIVERSAL DR-RESTRICTED HELPER EPITOPES BY MODIFICATION OF HIGH-AFFINITY DR-BLOCKING PEPTIDES

Pan DR-binding peptides engineered by introducing anchor residues for different DR motifs within a polyalanine backbone bound 10 of 10 DR mo lecules tested, with affinities, in most cases, in the nanomolar range . Because of the small methyl group exposed far T cell recognition, th ese peptides were poor immunogens but effective blockers of DR-restric ted antigen presentation. Introduction of bulky and charged residues a t positions accessible for T cell recognition yielded extremely powerf ul Pan DR epitope peptides (PADRE). These peptides elicited powerful r esponses in vitro from human peripheral blood mononuclear cells (PBMC) . Because these cells also cross-react on certain mouse class II allel es, we could also demonstrate that PADRE peptides are active in vivo. In one example of their capacity to elicit T help, they were approxima tely 1000 times more powerful than natural T cell epitopes. We propose that PADRE peptides may be useful in the development of subunit vacci nes.