Dominant CD8 T-Lymphocyte Responses Suppress Expansion of Vaccine-Elicited Subdominant T Lymphocytes in Rhesus Monkeys Challenged with Pathogenic Simian-Human

Emerging data suggest that a cytotoxic T-lymphocyte response against a diversity of epitopes confers greater protection against a human immunodeficiency virus/simian immunodeficiency virus infection than does a more focused response. To facilitate the creation of vaccine strategies that will generate cellular immune responses with the greatest breadth, it will be important to understand the mechanisms employed by the immune response to regulate the relative magnitudes of dominant and nondominant epitope-specific cellular immune responses. In this study, we generated dominant Gag p11C- and subdominant Env p41A-specific CD8 T-lymphocyte responses in Mamu-A*01 rhesus monkeys through vaccination with plasmid DNA and recom-binant adenovirus encoding simian-human immunodeficiency virus (SHIV) proteins. Infection of vaccinated Mamu-A*01 rhesus monkeys with a SHIV Gag p11C mutant virus generated a significantly increased expansion of the Env p41A-specific CD8 T-lymphocyte response in the absence of secondary Gag p11C-specific CD8 T-lymphocyte responses. These results indicate that the presence of the Gag p11C-specific CD8 T-lymphocyte response following virus challenge may exert suppressive effects on primed Env p41A-specific CD8 T-lymphocyte responses. These findings suggest that immunodomination exerted by dominant responses during SHIV infection may diminish the breadth of recall responses primed during vaccination. CD8 T lymphocyte responses play a central role in con