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

On Ho^* and William R. Green^1,*,

^* Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756; and Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. William R. Green, Dartmouth Medical School, Department of Microbiology and Immunology, 603W Borwell Building, One Medical Center Drive, Lebanon, NH 03756. E-mail address: william.r.green{at}dartmouth.edu

² Abbreviations used in this paper: DRiP, defective ribosomal product; ARF, alternative reading frame; HCV, hepatitis C virus; MAIDS, mouse AIDS; ORF, open reading frame; TIL, tumor-infiltrating lymphocyte; TK, thymidine kinase.

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