Journal
JOURNAL OF VIROLOGY
Volume 76, Issue 17, Pages 8690-8701Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.76.17.8690-8701.2002
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Funding
- NIAID NIH HHS [R01 AI030914, R01 AI44656, R01 AI30914, R01 AI50429, R37 AI125568, R01 AI040873, R01 AI40873, R01 AI050429, R01 AI044656] Funding Source: Medline
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Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T-cell responses generated during acute infection play a critical role in the initial control of viremia. However, little is known about the viral T-cell epitopes targeted during acute infection or about their hierarchy in appearance and relative immunodominance over time. In this study, HIV-1-specific CD8(+) T-cell responses in 18 acutely infected individuals expressing HLA-A3 and/or -B7 were characterized. Detailed analysis of CD8 responses in one such person who underwent treatment of acute infection followed by reexposure to HIV-1 through supervised treatment interruptions (STI) revealed recognition of only two cytotoxic T-lymphocyte (CTL) epitopes during symptomatic acute infection. HIV-1-specific CD8(+) T-cell responses broadened significantly during subsequent exposure to the virus, ultimately targeting 27 distinct CTL epitopes, including 1.5 different CTL epitopes restricted by a single HLA class I allele (HLA-A3). The same few peptides were consistently targeted in an additional 17 persons expressing HLA-A3 and/or -B7 during acute infection. These studies demonstrate a consistent pattern in the development of epitope-specific responses restricted by a single HLA allele during acute HIV-1 infection, as well as persistence of the initial pattern of immunodominance during subsequent STI. In addition, they demonstrate that HIV-1-specific CD8(+) T-cell responses can ultimately :target a previously unexpected and unprecedented number of epitopes in a single infected individual; even though these are not detectable during the initial exposure to virus. These studies have important implications for vaccine design and evaluation.
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