Alternative Translational Products and Cryptic T Cell Epitopes: Expecting the Unexpected

Although CD8 T cell epitopes have been studied extensively, often overlooked are unconventional cryptic epitopes generated from nontraditional sources of peptides/proteins and/or mechanisms of translation. In this review, we discuss alternative reading frame epitopes, both mechanistically and also in terms of their physiologic importance in the induction of antiviral and antitumor CTL responses. Issues of the influence of cryptic translational products on foreign and self-Ag diversity, thymic selection, and the T cell repertoire; disease pathogenesis; and approaches to vaccine design are discussed in context of the potentially large impact of unconventional epitopes on T cell immunity.