Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection

B. R. Mothé, H. Horton, D. K. Carter, T. M. Allen, M. E. Liebl, P. Skinner, T. U. Vogel, S. Fuenger, K. Vielhuber, W. Rehrauer, N. Wilson, G. Franchini, J. D. Altman, A. Haase, L. J. Picker, D. B. Allison, David Watkins

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)875-884
Number of pages10
JournalJournal of Virology
Volume76
Issue number2
DOIs
StatePublished - Jan 15 2002
Externally publishedYes

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Macaca
major histocompatibility complex
Cytotoxic T-Lymphocytes
Virus Diseases
Major Histocompatibility Complex
epitopes
dominance (genetics)
cytotoxic T-lymphocytes
Epitopes
Acute-Phase Reaction
immune response
Viruses
Macaca mulatta
T-Lymphocytes
T-lymphocytes
vif Gene Products
vpr Gene Products
nef Gene Products
rev Gene Products
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection. / Mothé, B. R.; Horton, H.; Carter, D. K.; Allen, T. M.; Liebl, M. E.; Skinner, P.; Vogel, T. U.; Fuenger, S.; Vielhuber, K.; Rehrauer, W.; Wilson, N.; Franchini, G.; Altman, J. D.; Haase, A.; Picker, L. J.; Allison, D. B.; Watkins, David.

In: Journal of Virology, Vol. 76, No. 2, 15.01.2002, p. 875-884.

Research output: Contribution to journalArticle

Mothé, BR, Horton, H, Carter, DK, Allen, TM, Liebl, ME, Skinner, P, Vogel, TU, Fuenger, S, Vielhuber, K, Rehrauer, W, Wilson, N, Franchini, G, Altman, JD, Haase, A, Picker, LJ, Allison, DB & Watkins, D 2002, 'Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection', Journal of Virology, vol. 76, no. 2, pp. 875-884. https://doi.org/10.1128/JVI.76.2.875-884.2002
Mothé, B. R. ; Horton, H. ; Carter, D. K. ; Allen, T. M. ; Liebl, M. E. ; Skinner, P. ; Vogel, T. U. ; Fuenger, S. ; Vielhuber, K. ; Rehrauer, W. ; Wilson, N. ; Franchini, G. ; Altman, J. D. ; Haase, A. ; Picker, L. J. ; Allison, D. B. ; Watkins, David. / Dominance of CD8 responses specific for epitopes bound by a single major histocompatibility complex class I molecule during the acute phase of viral infection. In: Journal of Virology. 2002 ; Vol. 76, No. 2. pp. 875-884.
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AU - Vogel, T. U.

AU - Fuenger, S.

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AU - Rehrauer, W.

AU - Wilson, N.

AU - Franchini, G.

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