Fusion of a cell penetrating peptide from HIV-1 TAT to the Theileria parva antigen Tp2 enhances the stimulation of bovine CD8+ T cell responses
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Tinega,, A.N.; Pellé, R..; Kang’a, S.; Gicheru,, M.M.; Taracha, E.L.N.; Nene, V.; Graham, S.P. 2009. Fusion of a cell penetrating peptide from HIV-1 TAT to the Theileria parva antigen Tp2 enhances the stimulation of bovine CD8+ T cell responses. Veterinary Immunology and Immunopathology (The Netherlands). v. 130(1-2). p. 107-113.
Permanent link to this item: http://hdl.handle.net/10568/50
Immunity to the bovine apicomplexan parasite Theileria parva is associated with MHC-I restricted CD8+ T cell responses directed against the intralymphocytic schizont stage of the parasite. A number of schizont-stage antigens that are targets of CD8+ T cell responses from immune animals have been identified but an effective delivery strategy that consistently induces protective CD8+ T cell responses remains to be developed. This study aimed to determine whether fusing Tat, a cell penetrating peptide (CPP) from HIV-1 TAT, to a CD8+ T cell target antigen from T. parva (Tp2) enhances the cytosolic delivery and subsequent stimulation of bovine CD8+ T cell responses in vitro. Using IFN-γ ELISpot and cytotoxicity assays, it was demonstrated that recombinant Tat-Tp2 fusion protein possessed a superior ability to access MHC-I processing and presentation pathway and to stimulate CD8+ T cell responses compared to recombinant Tp2 protein. Exposure of APC to Tat-Tp2 protein for only 30 min was sufficient for protein uptake and stimulation of CD8+ T cells. This work describes for the first time the utility of a CPP to enhance MHC-I presentation in a veterinary species and supports the evaluation of CPP fusion proteins in the induction of CD8+ T cell responses in vivo.
Alex N. Tinega, Roger Pellé, Evans L.N. Taracha & Simon P. Graham are ILRI authors.