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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 {triangledown} ,{dagger}

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. Kent1*

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.

* 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

{triangledown} Published ahead of print on 28 May 2008.

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

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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