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Gag-specific CD8(+) T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression

  1. Author:
    Sacha, J. B.
    Chung, C.
    Rakasz, E. G.
    Spencer, S. P.
    Jonas, A. K.
    Bean, A. T.
    Lee, W.
    Burwitz, B. J.
    Stephany, J. J.
    Loffredo, J. T.
    Allison, D. B.
    Adnan, S.
    Hoji, A.
    Wilson, N. A.
    Friedrich, T. C.
    Lifson, J. D.
    Yang, O. O.
    Watkins, D. I.

  2. Author Address

    Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53715 USA. Wisconsin Natl Primate Res Ctr, Madison, WI USA. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. Univ Calif Los Angeles, Geffen Sch Med, AIDS Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21702 USA.;Watkins, DI, Univ Wisconsin, Dept Pathol & Lab Med, 555 Sci Dr, Madison, WI 53711 USA.;watkins@primate.wisc.edu
    1. Year: 2007
    2. Date: Mar
  2. Journal: Journal of Immunology
    1. 178
    2. 5
    3. Pages: 2746-2754
  4. Type of Article: Article
  5. ISSN: 0022-1767
  1. Abstract:

    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.

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External Sources

  1. View record in Web of Science®
  2. WOS: 000244734500026

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