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* Wisconsin National Primate Research Center and
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715;
Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294;
AIDS Institute and Department of Medicine, Geffen School of Medicine, University of California, Los Angeles, CA 90095; and
¶ AIDS Vaccine Program, Science Applications International Corp. National Cancer Institute, Frederick, MD 21702
CD8+ T cells are a key focus of vaccine development efforts for HIV. However, there is no clear consensus as to which of the nine HIV proteins should be used for vaccination. The early proteins Tat, Rev, and Nef may be better CD8+ T cell targets than the late-expressed structural proteins Gag, Pol, and Env. In this study, we show that Gag-specific CD8+ T cells recognize infected CD4+ T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation. Additionally, the number of Gag epitopes recognized by CD8+ T cells was significantly associated with lower viremia (p = 0.0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8+ T cell responses on Gag.
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 This work was supported by National Institutes of Health Grants R01AI052056 and R01AI049120 (to D.I.W.) and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. This publication was also made possible in part by National Institutes of Health Grant P51RR000167 awarded to the Wisconsin National Primate Research Center. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program Grants RR15459-01 and RR020141-01.
2 Address correspondence and reprint requests to Dr. David I. Watkins, Department of Pathology and Laboratory Medicine, University of Wisconsin, 555 Science Drive, Madison, WI 53711. E-mail address: watkins{at}primate.wisc.edu
3 Abbreviations used in this paper: MHC-I, MHC class I; SEB, staphylococcal enterotoxin B; BFA, brefeldin A; ICS, intracellular cytokine staining; KICS, kinetic ICS.
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