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 molecules tested, with affinities, in most cases, in the nanomolar range. Because of the small methyl group exposed for T cell recognition, these peptides were poor immunogens but effective blockers of DR-restricted antigen presentation. Introduction of bulky and charged residues at positions accessible for T cell recognition yielded extremely powerful Pan DR epitope peptides (PADRE). These peptides elicited powerful responses in vitro from human peripheral blood mononuclear cells (PBMC). Because these cells also cross-react on certain mouse class II alleles, we could also demonstrate that PADRE peptides are active in vivo. In one example of their capacity to elicit T help, they were approximately 1000 times more powerful than natural T cell epitopes. We propose that PADRE peptides may be useful in the development of subunit vaccines.
Alexander
J
J
Cytel Corporation, San Diego, California 92121.
Sidney
J
J
Southwood
S
S
Ruppert
J
J
Oseroff
C
C
Maewal
A
A
Snoke
K
K
Serra
H M
HM
Kubo
R T
RT
Sette
A
A
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites; D002455:Cell Division; D003429:Cross Reactions; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D006684:HLA-DR Antigens; D010455:Peptides