title: Vaccine-induced CD8+ T lymphocytes of rhesus monkeys recognize variant forms of an HIV epitope but do not mediate optimal functional activity.
abstract: The sequence diversity of HIV-1 presents a challenge for the development of an effective HIV-1 vaccine, because such a vaccine must confer protection against diverse forms of the virus. The present studies were initiated to explore how vaccine-induced clonal populations of CD8(+) T lymphocytes of rhesus monkeys recognize variants of an HIV-1 envelope epitope sequence. Evaluating a subset of variants of a selected epitope peptide that retain their binding to the MHC class I molecule of rhesus monkeys that presents this epitope peptide, we show that vaccine-elicited CD8(+) T lymphocytes comparably recognize the wild-type and a number of variant epitope peptides as determined by tetramer binding assays. In fact, the same clonal populations of CD8(+) T lymphocytes recognize the wild-type and variant epitope peptides. However, functional assays show that many of these variant epitope peptides stimulate suboptimal cytokine production by the vaccine-elicited CD8(+) T lymphocytes. These findings suggest that vaccine-induced CD8(+) T lymphocyte populations may recognize diverse forms of a viral epitope, but may not function optimally to confer protection against viruses expressing many of those variant sequences.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Sandrine L
authors.initials: SL
authors.lastname: Hulot
authors.forename: Evan M
authors.initials: EM
authors.lastname: Cale
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015700:HIV Envelope Protein gp41