Development of high potency universal DR-restricted helper epitopes by modification of high affinity DR-blocking peptides

Immunity. 1994 Dec;1(9):751-61. doi: 10.1016/s1074-7613(94)80017-0.


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.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Binding Sites
  • Cell Division
  • Cross Reactions
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation
  • Mice
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / immunology*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • HLA-DR Antigens
  • Peptides