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Journal of Virology, February 2001, p. 1301-1311, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1301-1311.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of Novel HLA-A2-Restricted Human Immunodeficiency Virus Type 1-Specific Cytotoxic T-Lymphocyte Epitopes Predicted by the HLA-A2 Supertype Peptide-Binding Motif

Marcus A. Altfeld,1 Brian Livingston,2 Neha Reshamwala,1 Phuong T. Nguyen,1 Marylyn M. Addo,1 Amy Shea,1 Mark Newman,2 John Fikes,2 John Sidney,2 Peggy Wentworth,2 Robert Chesnut,2 Robert L. Eldridge,1 Eric S. Rosenberg,1 Gregory K. Robbins,1 Christian Brander,1 Paul E. Sax,3 Steve Boswell,4 Theresa Flynn,1 Susan Buchbinder,5 Philip J. R. Goulder,1 Bruce D. Walker,1 Alessandro Sette,2 and Spyros A. Kalams1,*

Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School,1 Department of Medicine, Brigham and Women's Hospital and Harvard Medical School,3 and Fenway Community Health Center,4 Boston, Massachusetts, and Epimmune, Inc., San Diego,2 and AIDS Office, Department of Public Health, San Francisco,5 California

Received 1 August 2000/Accepted 30 October 2000

Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to assess in immunogenicity studies in infected persons and in uninfected recipients of candidate HIV-1 vaccines.

* Corresponding author. Mailing address: MGH-East, CNY, 5th Floor, 149 13th St., Charlestown, MA 02129. Phone: (617) 726-8166. Fax: (617) 726-5411. E-mail: kalams{at}helix.mgh.harvard.edu.

Journal of Virology, February 2001, p. 1301-1311, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1301-1311.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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