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Journal of Virology, October 2000, p. 9144-9151, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Putative Immunodominant Human Immunodeficiency Virus-Specific CD8+ T-Cell Responses Cannot Be Predicted by Major Histocompatibility Complex Class I Haplotype

Michael R. Betts,1 Joseph P. Casazza,1 Brent A. Patterson,1 Shar Waldrop,2 Wendy Trigona,3 Tong-Ming Fu,3 Florian Kern,4 Louis J. Picker,2 and Richard A. Koup1,*

Department of Internal Medicine, Division of Infectious Diseases, The University of Texas Southwestern Medical Center, Dallas, Texas 753901; Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Portland, Oregon 97201-30982; Merck Research Laboratories, West Point, Pennsylvania 194863; and Institute for Medical Immunology, Charité, Humboldt Universität zu Berlin, 10098 Berlin, Germany4

Received 25 April 2000/Accepted 26 June 2000

Recent studies of human immunodeficiency virus (HIV)-specific CD8+ T cells have focused on responses to single, usually HLA-A2-restricted epitopes as surrogate measures of the overall response to HIV. However, the assumption that a response to one epitope is representative of the total response is unconfirmed. Here we assess epitope immunodominance and HIV-specific CD8+ T-cell response complexity using cytokine flow cytometry to examine CD8+ T-cell responses in 11 HLA-A2+ HIV+ individuals. Initial studies demonstrated that only 4 of 11 patients recognized the putative immunodominant HLA-A2-restricted p17 epitope SLYNTVATL, suggesting that the remaining subjects might lack significant HIV-specific CD8+ T-cell responses. However, five of six SLYNTVATL nonresponders recognized other HIV epitopes, and two of four SLYNTVATL responders had greater responses to HIV peptides restricted by other class I alleles. In several individuals, no HLA-A2-restricted epitopes were recognized, but CD8+ T-cell responses were detected to epitopes restricted by other HLA class I alleles. These data indicate that an individual's overall CD8+ T-cell response to HIV is not adequately represented by the response to a single epitope and that individual major histocompatibility complex class I alleles do not predict an immunodominant response restricted by that allele. Accurate quantification of total HIV-specific CD8+ T-cell responses will require assessment of the response to all possible epitopes.

* Corresponding author. Mailing address: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9113. Phone: (214) 648-2807. Fax: (214) 648-2431. E-mail: richard.koup{at}emailswmed.edu.

Journal of Virology, October 2000, p. 9144-9151, Vol. 74, No. 19
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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