This delay in kinetics was not due to differences in viral load kinetics or magnitude or in viral escape mutations, but was associated with the evolution of the Mamu-A*01-restricted CD8 + T lymphocyte responses to the highly dominant SIV epitopes Gag p11C and Tat TL8. The Mamu-A*02 + monkeys that also expressed Mamu-A*01 exhibited a significant delay in the evolution of the CD8 + T lymphocyte responses specific for the dominant Mamu-A*02-restricted SIV epitope, Nef p199RY. To explore this biology, we identified cohorts of rhesus monkeys that expressed the MHC class I molecules Mamu-A*01, Mamu-A*02, or both, and assessed the evolution of their dominant epitope-specific CD8 + T lymphocyte responses (Gag p11C- and Tat TL8-specific in the Mamu-A*01 + and Nef p199RY-specific in the Mamu-A*02 + monkeys) following acute SIV infection. Developing strategies to elicit such broad immune responses will require an understanding of the mechanisms responsible for focusing CD8 + T lymphocyte recognition on a limited number of epitopes. Because the control of HIV-1 replication is largely dependent on CD8 + T lymphocyte responses specific for immunodominant viral epitopes, vaccine strategies that increase the breadth of dominant epitope-specific responses should contribute to containing HIV-1 spread.
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