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One essential component of our biodefense and preparedness efforts is an understanding of poxvirus immunity. To this end a number of laboratories have sought to discover T\u2010 and B\u2010Cell epitopes from select agents such as <jats:italic>variola virus<\/jats:italic>. This review focuses on the efforts to identify CD8<jats:sup>+<\/jats:sup> T\u2010Cell epitopes from poxviruses as a means to develop new vaccines and therapeutics. A wide variety of techniques have been employed by several research groups to provide complementary information regarding cellular immune responses to poxviruses. In the last several years well over 100 T\u2010Cell epitopes have been identified and the work rapidly continues. The information gleaned from these studies will not only give us a greater understanding of immunity to <jats:italic>variola virus<\/jats:italic> and other viruses, but also provide a foundation for next generation vaccines and additional tools with which to study host\u2010pathogen interactions. 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