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Journal of Virology, January 2002, p. 875-884, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.875-884.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Dominance of CD8 Responses Specific for Epitopes Bound by a Single Major Histocompatibility Complex Class I Molecule during the Acute Phase of Viral Infection

Bianca R. Mothé,1,2 Helen Horton,1 Donald K. Carter,1 Todd M. Allen,1 Max E. Liebl,1 Pam Skinner,3 Thorsten U. Vogel,1 Sarah Fuenger,1 Kathy Vielhuber,1 William Rehrauer,1 Nancy Wilson,1 Genoveffa Franchini,4 John D. Altman,5 Ashley Haase,3 Louis J. Picker,6 David B. Allison,7 and David I. Watkins1,2*

Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715,1 Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 53792,2 Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455,3 Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892,4 Emory Vaccine Center, Atlanta, Georgia 30329,5 Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Portland, Oregon 97201,6 Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 352947

Received 25 July 2001/ Accepted 3 October 2001

Cytotoxic T-lymphocyte (CTL) responses are thought to control human immunodeficiency virus replication during the acute phase of infection. Understanding the CD8+ T-cell immune responses early after infection may, therefore, be important to vaccine design. Analyzing these responses in humans is difficult since few patients are diagnosed during early infection. Additionally, patients are infected by a variety of viral subtypes, making it hard to design reagents to measure their acute-phase immune responses. Given the complexities in evaluating acute-phase CD8+ responses in humans, we analyzed these important immune responses in rhesus macaques expressing a common rhesus macaque major histocompatibility complex class I molecule (Mamu-A*01) for which we had developed a variety of immunological assays. We infected eight Mamu-A*01-positive macaques and five Mamu-A*01-negative macaques with the molecularly cloned virus SIVmac239 and determined all of the simian immunodeficiency virus-specific CD8+ T-cell responses against overlapping peptides spanning the entire virus. We also monitored the evolution of particular CD8+ T-cell responses by tetramer staining of peripheral lymphocytes as well as lymph node cells in situ. In this first analysis of the entire CD8+ immune response to autologous virus we show that between 2 and 12 responses are detected during the acute phase in each animal. CTL against the early proteins (Tat, Rev, and Nef) and against regulatory proteins Vif and Vpr dominated the acute phase. Interestingly, CD8+ responses against Mamu-A*01-restricted epitopes Tat28-35SL8 and Gag181-189CM9 were immunodominant in the acute phase. After the acute phase, however, this pattern of reactivity changed, and the Mamu-A*01-restricted response against the Gag181-189CM9 epitope became dominant. In most of the Mamu-A*01-positive macaques tested, CTL responses against epitopes bound by Mamu-A*01 dominated the CD8+ cellular immune response.

* Corresponding author. Mailing address: Wisconsin Regional Primate Research Center, 1220 Capitol Ct., Madison, WI 53715-1299. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu.

Journal of Virology, January 2002, p. 875-884, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.875-884.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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