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Consistent Patterns in the Development and Immunodominance of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8 + T-Cell Responses following Acute HIV-1 Infection

2002; American Society for Microbiology; Volume: 76; Issue: 17 Linguagem: Inglês

10.1128/jvi.76.17.8690-8701.2002

1098-5514

Xu G. Yu, Marylyn M. Addo, Eric Rosenberg, William Rodriguez, Paul K. Lee, Cecily A. Fitzpatrick, Mary N. Johnston, Daryld Strick, Philip Goulder, Bruce D. Walker, Marcus Altfeld,

T-cell and B-cell Immunology

ABSTRACT 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 15 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.