title: Dominant CD8+ T-lymphocyte responses suppress expansion of vaccine-elicited subdominant T lymphocytes in rhesus monkeys challenged with pathogenic simian-human immunodeficiency virus.
abstract: 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 recombinant adenovirus encoding simian-human immunodeficiency virus (SHIV) proteins. Infection of vaccinated Mamu-A*01(+) rhesus monkeys with a SHIV Gag Deltap11C 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.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, E/CLS Room 1043, Boston, Massachusetts 02215, USA.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Manuel
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Yeh
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Kathryn
authors.initials: K
authors.lastname: Furr
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lifton
authors.forename: Sandrine L
authors.initials: SL
authors.lastname: Hulot
authors.forename: Patrick
authors.initials: P
authors.lastname: Autissier
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000483:Alleles; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry; D005434:Flow Cytometry / Q000379:methods; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics*; D008253:Macaca mulatta; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D017354:Point Mutation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
chemical_list: D000939:Epitopes; D015683:Gene Products, gag; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018449:SAIDS Vaccines