INTRODUCTION: Induction of a protective immune response against requires the activation of both TH1 and CD8 T lymphocytes. Because is an intra-phagosomal parasite, its antigens do not have access to MHC-I. The present study aimed to evaluate the effect of cysteine peptidase A (CPA)/cysteine peptidase B (CPB) conjugated to α-AL2O3 on autophagy induction in infected macrophages and subsequent activation of cytotoxic CD8 T lymphocytes. METHODS: Recombinant CPA and CPB of were produced in expression vectors and purified. Aldehyde functionalized α-AL2O3 were conjugated to hydrazine-modified CPA/CPB by a chemical bond was confirmed by Fourier-transform infrared spectroscopy (FTIR). The High efficient internalization of α-AL2O3 conjugated CPA/CPB to macrophages was confirmed using a fluorescence microscope and flowcytometry. Induction of the acidic autophagosome and LC3 conversion in macrophages was determined by acridine orange (AO) staining and western blot. Autophagy-activated macrophages were used for CD8 T cell priming. Cytotoxic activity of the primed CD8 T cell against infected macrophages was measured using apoptosis assay. RESULTS: α-AL2O3 conjugated CPA/CPB enhances macrophages antigen uptake and increases acidic vacuole formation and LC-3I to LC-3II conversion. Co-culture of autophagy-activated macrophages with CD8 T cells augmented CD8 T cells priming and proliferation more than in other study groups. These primed CD8 T cells induce significant apoptotic death of infected macrophages compared with non-primed CD8 T cells. CONCLUSION: α-AL2O3 nanoparticles enhance the cross-presentation of antigens to CD8 T cells by inducing autophagy. This finding supports the positive role of autophagy and encourages the use of α-AL2O3 in vaccine design.