HHD mice which express human HLA-A2 but no mouse class I, have been shown to have improved cytotoxic lymphocyte (CTL) responses to foreign antigens compared to HLA*A201/Kb transgenic mice. We have previously designed a DNA vaccine to a self antigen. Vaccination of A2.1/H-2Kb mice with this vaccine resulted in CTL in one third of the mice, but the frequency of antigen-specific cells was low. An increased frequency was observed in HHD mice, moreover CTL were obtained from all immunised mice. HHD mice are therefore useful for studying immunisation strategies for inducing and maintaining CD8 responses to over-expressed self antigens.