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Journal of Virology, March 2007, p. 2440-2448, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01847-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

CD8 T-Cell Recognition of Multiple Epitopes within Specific Gag Regions Is Associated with Maintenance of a Low Steady-State Viremia in Human Immunodeficiency Virus Type 1-Seropositive Patients{triangledown}

Christof Geldmacher,1,2* Jeffrey R. Currier,3 Eva Herrmann,6 Antelmo Haule,1 Ellen Kuta,3 Francine McCutchan,3 Lilian Njovu,1 Steffen Geis,1 Oliver Hoffmann,1 Leonard Maboko,1 Carolyn Williamson,4 Deborah Birx,3 Andreas Meyerhans,5 Josephine Cox,3 and Michael Hoelscher2

Mbeya Medical Research Programme, Referral Hospital, Mbeya, Tanzania,1 Department of Infectious Diseases and Tropical Medicine, University of Munich, 80799 Munich, Germany,2 U.S. Military HIV Research Program, Rockville, Maryland 20851,3 Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa,4 Institute of Virology, University of Saarland, 66421 Homburg, Germany,5 Department of Internal Medicine, University of Saarland, 66421 Homburg, Germany6

Received 24 August 2006/ Accepted 27 November 2006

The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted. While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles. In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HLA class I alleles in a cohort of HIV-seropositive bar workers. Possession of the HLA class I alleles B5801, B8101, and B0702 was associated with a low median viral load and simultaneously with a broader median recognition of Gag epitopes compared to all other HLA alleles (twofold increase) (P = 0.0035). We further found an inverse linear relationship between the number of Gag epitopes recognized and the plasma viral load (R = –0.36; P = 0.0016). Particularly, recognition of multiple epitopes within two regions of Gag (amino acids [aa] 1 to 75 and aa 248 to 500) was associated with the maintenance of a low steady-state viremia, even years after acute infection.

* Corresponding author. Present address: Vaccine Research Center, NIAID, Bethesda, MD 20892. Phone: (301) 594-8619. Fax: (301) 480-2779. E-mail: cgeldmacher{at}mmrp.org.

{triangledown} Published ahead of print on 20 December 2006.

Journal of Virology, March 2007, p. 2440-2448, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.01847-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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