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Journal of Virology, September 2002, p. 8690-8701, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8690-8701.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Xu G. Yu,1,2 Marylyn M. Addo,1,2 Eric S. Rosenberg,1,2 William R. Rodriguez,1,2 Paul K. Lee,1,2 Cecily A. Fitzpatrick,1,2 Mary N. Johnston,1,2 Daryld Strick,1,2 Philip J. R. Goulder,1,2,3 Bruce D. Walker,1,2 and Marcus Altfeld1,2*

Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital,1 Division of AIDS, Harvard Medical School, Boston, Massachusetts,2 Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom3

Received 6 March 2002/ Accepted 21 May 2002

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.

* Corresponding author. Mailing address: Massachusetts General Hospital East, CNY 5212, 149 13th St., Charlestown, MA 02129. Phone: (617) 724-2461. Fax: (617) 726-5411. E-mail: Maltfeld{at}partners.org.

Journal of Virology, September 2002, p. 8690-8701, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8690-8701.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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