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Journal of Virology, July 2001, p. 6279-6291, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6279-6291.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Relative Dominance of Epitope-Specific Cytotoxic T-Lymphocyte Responses in Human Immunodeficiency Virus Type 1-Infected Persons with Shared HLA Alleles

Cheryl L. Day,1 Amy K. Shea,1 Marcus A. Altfeld,1 Douglas P. Olson,1 Susan P. Buchbinder,2 Frederick M. Hecht,3 Eric S. Rosenberg,1 Bruce D. Walker,1 and Spyros A. Kalams1,*

Partners AIDS Research Center, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 021141; AIDS Office, Department of Public Health, Division of AIDS, San Francisco, California 941202; and Positive Health Program, University of California at San Francisco, San Francisco, California 941433

Received 13 March 2001/Accepted 24 April 2001

Cytotoxic T lymphocytes (CTL) target multiple epitopes in human immunodeficiency virus (HIV)-infected persons, and are thought to influence the viral set point. The extent to which HLA class I allele expression predicts the epitopes targeted has not been determined, nor have the relative contributions of responses restricted by different class I alleles within a given individual. In this study, we performed a detailed analysis of the CTL response to optimally defined CTL epitopes restricted by HLA class I A and B alleles in individuals who coexpressed HLA A2, A3, and B7. The eight HIV-1-infected subjects studied included two subjects with acute HIV infection, five subjects with chronic HIV infection, and one long-term nonprogressor. Responses were heterogeneous with respect to breadth and magnitude of CTL responses in individuals of the same HLA type. Of the 27 tested epitopes that are presented by A2, A3, and B7, 25 were targeted by at least one person. However, there was wide variation in the number of epitopes targeted, ranging from 2 to 17. The A2-restricted CTL response, which has been most extensively studied in infected persons, was found to be narrowly directed in most individuals, and in no cases was it the dominant contributor to the total HIV-1-specific CTL response. These results indicate that HLA type alone does not predict CTL responses and that numerous potential epitopes may not be targeted by CTL in a given individual. These data also provide a rationale for boosting both the breadth and the magnitude of HIV-1-specific CTL responses by immunotherapy in persons with chronic HIV-1 infection.

* Corresponding author. Mailing address: Massachusetts General Hospital, AIDS Research Center, 149 13th Street, Rm. 5217, Charlestown, MA 02129. Phone: (617) 724-4958. Fax: (617) 726-4691. E-mail: kalams{at}helix.mgh.harvard.edu.

Journal of Virology, July 2001, p. 6279-6291, Vol. 75, No. 14
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.14.6279-6291.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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