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

Autor: Roger Pelle, Vishvanath Nene, Simon P. Graham, Michael M. Gicheru, Simon Kang’a, Alex N. Tinega, Evans L. N. Taracha
Rok vydání: 2009
Předmět:
Zdroj: Veterinary Immunology and Immunopathology. 130:107-113
ISSN: 0165-2427
DOI: 10.1016/j.vetimm.2009.01.008
Popis: 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.
Databáze: OpenAIRE