HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ho, O. Articles by Green, W. R. Search for Related Content PubMed PubMed Citation Articles by Ho, O. Articles by Green, W. R.

Cytolytic CD8⁺ T Cells Directed against a Cryptic Epitope Derived from a Retroviral Alternative Reading Frame Confer Disease Protection¹

On Ho^* and William R. Green^2,*,

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

Cytolytic CD8⁺ T cells (CTL) are key to the immune response that controls virus infections and mediates disease protection. The ability of CTL to induce apoptosis of infected cells and/or limit viral replication is determined by recognition of processed viral peptide epitopes on the surface of the target cell. An understudied source of MHC class I-presented peptides is the aptly named "cryptic epitopes," defined by their nontraditional methods of generation, including derivation from alternative reading frames (ARFs). Although ARF-encoded epitopes have now been documented in a few systems, their potential functional relevance in vivo has been debated. In this study, we demonstrate the physiological significance of an ARF-derived CTL epitope in a retrovirus-induced disease model. We show that disease-susceptible CD8-deficient mice reconstituted with CTL specific for the retroviral ARF-derived SYNTGRFPPL epitope controlled an infection by the LP-BM5 retrovirus isolate, evidently at the level of viral clearance, resulting in protection of these mice from disease. These data indicate that ARF-derived epitopes are indeed relevant inducers of the immune system and demonstrate the importance of atypically generated peptides as functional Ag with a physiologic role in disease protection.

This article has been cited by other articles:

				K. E. Garrison, S. Champiat, V. A. York, A. T. Agrawal, E. G. Kallas, J. N. Martin, F. M. Hecht, S. G. Deeks, and D. F. Nixon Transcriptional Errors in Human Immunodeficiency Virus Type 1 Generate Targets for T-Cell Responses Clin. Vaccine Immunol., September 1, 2009; 16(9): 1369 - 1371. [Abstract] [Full Text] [PDF]

				K. A. Green, T. Okazaki, T. Honjo, W. J. Cook, and W. R. Green The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome J. Virol., March 1, 2008; 82(5): 2456 - 2469. [Abstract] [Full Text] [PDF]

				N. J. Maness, L. E. Valentine, G. E. May, J. Reed, S. M. Piaskowski, T. Soma, J. Furlott, E. G. Rakasz, T. C. Friedrich, D. A. Price, et al. AIDS virus specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape J. Exp. Med., October 29, 2007; 204(11): 2505 - 2512. [Abstract] [Full Text] [PDF]

				O. Ho and W. R. Green Alternative Translational Products and Cryptic T Cell Epitopes: Expecting the Unexpected J. Immunol., December 15, 2006; 177(12): 8283 - 8289. [Abstract] [Full Text] [PDF]

				M. B. Zook, M. T. Howard, G. Sinnathamby, J. F. Atkins, and L. C. Eisenlohr Epitopes Derived by Incidental Translational Frameshifting Give Rise to a Protective CTL Response. J. Immunol., June 1, 2006; 176(11): 6928 - 6934. [Abstract] [Full Text] [PDF]