title: Enhanced immunogenicity of a T cell immunogenic peptide by modifications of its N and C termini.
abstract: The modification of the terminal ionizable charges of an immunogenic peptide, HEL (46-61), was found to greatly increase the immunogenicity of the peptide. The modified peptide had 100- to 1000-fold enhanced activity in both in vitro and in vivo T cell assays. The mechanism of the enhancement was investigated by determining the binding affinities to I-Ak as well as circular dichroism (CD) studies. The native and enhanced peptides had indistinguishable binding affinities, as well as similar kinetics. The CD studies revealed that in aqueous solution, neither peptide had any detectable helicity; however, the addition of trifluoroethanol did result in significant helicity; with the two peptides being indistinguishable. These same modifications were also shown to enhance other immunogenic peptides if they contained a basic carboxy-terminal amino acid residue. Thus, by modifying the termini of T cell epitopes, their immunogenicity can be dramatically increased, but the molecular basis for this enhancement is still unclear.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St Louis, MO 63110.
authors.forename: P M
authors.initials: PM
authors.lastname: Allen
authors.forename: G R
authors.initials: GR
authors.lastname: Matsueda
authors.forename: S
authors.initials: S
authors.lastname: Adams
authors.forename: J
authors.initials: J
authors.lastname: Freeman
authors.forename: R W
authors.initials: RW
authors.lastname: Roof
authors.forename: L
authors.initials: L
authors.lastname: Lambert
authors.forename: E R
authors.initials: ER
authors.lastname: Unanue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry; D000949:Histocompatibility Antigens Class II; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D009113:Muramidase