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Journal of Virology, August 2008, p. 7357-7368, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00607-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Limited Maintenance of Vaccine-Induced Simian Immunodeficiency Virus-Specific CD8 T-Cell Receptor Clonotypes after Virus Challenge ^,

Miranda Z. Smith,¹ Tedi E. Asher,² Vanessa Venturi,³ Miles P. Davenport,³ Daniel C. Douek,² David A. Price,^2,4 and Stephen J. Kent^1*

Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia,¹ Vaccine Research Centre, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,² Centre for Vascular Research, UNSW, Sydney, Australia,³ Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, United Kingdom⁴

Received 18 March 2008/ Accepted 16 May 2008

T-cell receptors (TCRs) govern the specificity, efficacy, and cross-reactivity of CD8 T cells. Here, we studied CD8 T-cell clonotypes from Mane-A*10⁺ pigtail macaques responding to the simian immunodeficiency virus (SIV) Gag KP9 epitope in a setting of vaccination and subsequent viral challenge. We observed a diverse TCR repertoire after DNA, recombinant poxvirus, and live attenuated virus vaccination, with none of 59 vaccine-induced KP9-specific TCRs being identical between macaques. The KP9-specific TCR repertoires remained diverse after SIV or simian-human immunodeficiency virus challenge but, remarkably, exhibited substantially different clonotypic compositions compared to the corresponding populations prechallenge. Within serial samples from individual pigtail macaques, only a small subset (33.9%) of TCRs induced by vaccination were maintained or expanded after challenge. Most (66.1%) of the TCRs induced by vaccination were not detectable after challenge. Our results suggest that some CD8 T cells induced by vaccination are more efficient than others at responding to a viral challenge. These findings have implications for future AIDS virus vaccine studies, which should consider the "fitness" of vaccine-induced T cells in order to generate robust responses in the face of virus exposure.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Melbourne 3010, Australia. Phone: 61-383449939. Fax: 61-383443846. E-mail: skent{at}unimelb.edu.au

Published ahead of print on 28 May 2008.

Supplemental material for this article may be found at http://jvi.asm.org/.

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Journal of Virology, August 2008, p. 7357-7368, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00607-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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