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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

Author:
Tinega, Alex N., Pellé, Roger, Kang'a, Simon, Gicheru, Michael M., Taracha, Evans L.N., Nene, Vishvanath, Graham, Simon P.
Source:
Veterinary immunology and immunopathology 2009 v.130 no.1-2 pp. 107-113
ISSN:
0165-2427
Subject:
cattle diseases, Human immunodeficiency virus 1, antigens, schizonts, recombinant proteins, cattle, peptides, major histocompatibility complex, theileriosis, viral proteins, immunostimulants, Theileria parva, in vitro studies, vaccine development, disease resistance, antigen-antibody reactions, CD8-positive T-lymphocytes
Abstract:
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 30min 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.
Agid:
758262