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Journal of Virology, April 2007, p. 4199-4214, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.01388-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Selective Depletion of High-Avidity Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8⁺ T Cells after Early HIV-1 Infection

Mathias Lichterfeld,^1, Xu G. Yu,^1, Stanley K. Mui,¹ Katie L. Williams,¹ Alicja Trocha,^1,2 Mark A. Brockman,^1,2 Rachel L. Allgaier,¹ Michael T. Waring,^1,2 Tomohiko Koibuchi,^1,2 Mary N. Johnston,¹ Daniel Cohen,³ Todd M. Allen,¹ Eric S. Rosenberg,¹ Bruce D. Walker,^1,2 and Marcus Altfeld^1*

Partners AIDS Research Center, Massachusetts General Hospital, and Division of AIDS, Harvard Medical School, Boston, Massachusetts,¹ Howard Hughes Medical Institute, Chevy Chase, Maryland,² Fenway Community Health, Boston, Massachusetts³

Received 2 July 2006/ Accepted 28 January 2007

Human immunodeficiency virus type 1 (HIV-1)-specific CD8⁺ T cells in early infection are associated with the dramatic decline of peak viremia, whereas their antiviral activity in chronic infection is less apparent. The functional properties accounting for the antiviral activity of HIV-1-specific CD8⁺ T cells during early infection are unclear. Using cytokine secretion and tetramer decay assays, we demonstrated in intraindividual comparisons that the functional avidity of HIV-1-specific CD8⁺ T cells was consistently higher in early infection than in chronic infection in the presence of high-level viral replication. This change of HIV-1-specific CD8⁺ T-cell avidity between early and chronic infections was linked to a substantial switch in the clonotypic composition of epitope-specific CD8⁺ T cells, resulting from the preferential loss of high-avidity CD8⁺ T-cell clones. In contrast, the maintenance of the initially recruited clonotypic pattern of HIV-1-specific CD8⁺ T cells was associated with low-level set point HIV-1 viremia. These data suggest that high-avidity HIV-1-specific CD8⁺ T-cell clones are recruited during early infection but are subsequently lost in the presence of persistent high-level viral replication.

Published ahead of print on 7 February 2007.

M.L. and X.G.Y. contributed equally to this work.

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