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Journal of Virology, December 2002, p. 12603-12610, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12603-12610.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8⁺-T-Cell Responses for Groups of HIV-1-Infected Individuals with Different HLA-B*35 Genotypes

Xia Jin,^1* Xiaojiang Gao,² Murugappan Ramanathan, Jr.,³ Geoffrey R. Deschenes,³ George W. Nelson,² Stephen J. O'Brien,⁴ James J. Goedert,⁵ David D. Ho,³ Thomas R. O'Brien,⁵ and Mary Carrington²

University of Rochester Medical Center, Rochester, New York 14642,¹ Intramural Research Support Program, SAIC,² Laboratory of Genomic Diversity, NCI—Frederick, Frederick, Maryland 21702,⁴ Aaron Diamond AIDS Research Center, New York, New York 10021,³ Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852⁵

Received 3 May 2002/ Accepted 29 August 2002

Human immunodeficiency virus type 1 (HIV-1)-infected individuals with HLA-B*35 allelic variants B*3502/3503/3504/5301 (B*35-Px) progress more rapidly to AIDS than do those with B*3501 (B*35-PY). The mechanisms responsible for this phenomenon are not clear. To examine whether cellular immune responses may differ according to HLA-B*35 genotype, we quantified HIV-1-specific CD8⁺-T-cell (CTL) responses using an intracellular cytokine-staining assay with specimens from 32 HIV-1-positive individuals who have B*35 alleles. Among them, 75% had CTL responses to Pol, 69% had CTL responses to Gag, 50% had CTL responses to Nef, and 41% had CTL responses to Env. The overall magnitude of CTL responses did not differ between patients bearing B*35-Px genotypes and those bearing B*35-PY genotypes. A higher percentage of Gag-specific CTL was associated with lower HIV-1 RNA levels (P = 0.009) in individuals with B*35-PY. A negative association between CTL activity for each of the four HIV antigens and viral load was observed among individuals with B*35-PY, and the association reached significance for Gag. No significant relationship between CTL activity and viral load was observed in the B*35-Px group. The relationship between total CTL activity and HIV RNA among B*35-Px carriers differed significantly from that among B*35-PY carriers (P < 0.05). The data are consistent with the hypothesis that higher levels of virus-specific CTL contribute to protection against HIV disease progression in infected individuals with B*35-PY, but not in those with B*35-Px.

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* Corresponding author. Mailing address: Infectious Disease Unit, University of Rochester Medical Center, 601 Elmwood Ave., Box 689, Rochester, NY 14642. Phone: (716) 275-6515. Fax: (716) 442-9328. E-mail: Xia_Jin{at}URMC.Rochester.edu.

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Journal of Virology, December 2002, p. 12603-12610, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12603-12610.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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