Its well accepted that the role of generation of tumor specific allo-reactive CD8+ T cells in tumor tolerance circumventing.Here, we generate allo-restricted peptide-specific CD8+ T cells by co-culture of lymphocytes and autologous monocytes bearing allogeneic HLA-A2 molecule associated with its restricted peptide.The monocytes were coated with the allogeneic epitope by binding of a dimeric HLA-A2/lgG1-Fc fusion protein (the dimer) to HLA-A2 negative (HLA-A2-ve) monocytes.An increased proliferation of CD8+T cells and induction of CTLs cells appeared after co-culturing of HLA-A2-ve lymphocytes and the autologous monocytes loaded with the dimer.The co-cultural bulks showed an increased frequency of the specific dimer-stained CD8+ T cells and the expanded CD8+ T cells exhibited an elevated IFN-γ production in response to specific TCR ligand.Tumor rejection effects of the allo-restricted AFP-specific CD8+ T cells raised by the co-culture were observed in nude mice challenged with human hepatocellular carcinoma cell HepG2 expressing both HLA-A2 and AFP antigens, which may contribute to the observations that the tumor avoidance and lifespan of the mice were improved after adoptive transfer of the CD8+ T cells.This study may offer a new opportunity to address this unmet medical need in separating graft-versus-leukemia or graft-versus-tumor reaction from graft-versus-host disease, and represent an attractive strategies for adding to the pool of human high-avidity TCRs specific for tumor or virus antigens.