In vivo generation of cytotoxic T cells from epitopes displayed on peptide-based delivery vehicles.
The development of nonviral, peptide-based constructs able to elicit protective in vivo CTL responses represents a major challenge in the design of future vaccines. We report the design of branched peptide delivery vehicles, termed loligomers, that facilitate the import, processing, and presentation of CTL epitopes onto nascent MHC class I molecules. These complexes are then effectively displayed on the surface of APCs. The intracellular delivery of CTL epitopes by loligomers prolonged the expression of Ag-MHC class I complexes on the surface of APCs in comparison with free CTL epitope alone. Furthermore, the injection of CTL epitope-containing loligomers into mice led to the generation of in vivo CTL responses and the induction of autoimmune disease in an animal model. Synthetic epitope-carrying, peptide-based delivery vehicles may represent useful components to be included in the formulation of future vaccines.
Kawamura
Kim S
KS
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Su
Ruey-Chyi
RC
Nguyen
Linh T
LT
Elford
Alisha R
AR
Ohashi
Pamela S
PS
Gariépy
Jean
J
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000502:physiology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D014677:Pharmaceutical Vehicles; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D014677:Pharmaceutical Vehicles