title: Diverse cross-reactive potential and Vbeta gene usage of an epitope-specific cytotoxic T-lymphocyte population in monkeys immunized with diverse human immunodeficiency virus type 1 Env immunogens.
abstract: An ideal human immunodeficiency virus type 1 (HIV-1) vaccine would elicit potent cellular and humoral immune responses that recognize diverse strains of the virus. In the present study, combined methodologies (flow cytometry, Vbeta repertoire analysis, and complementarity-determining region 3 sequencing) were used to determine the clonality of CD8(+) T lymphocytes taking part in the recognition of variant epitope peptides elicited in Mamu-A*01-positive rhesus monkeys immunized with vaccines encoding diverse HIV-1 envelopes (Envs). Monkeys immunized with clade B Envs generated CD8(+) T lymphocytes that cross-recognized both clade B- and clade C-p41A epitope peptides using a large degree of diversity in Vbeta gene usage. However, with two monkeys immunized with clade C Env, one monkey exhibited p41A-specific cytotoxic T-lymphocytes (CTL) with the capacity for cross-recognition of variant epitopes, while the other monkey did not. These studies demonstrate that the cross-reactive potential of variant p41A epitope peptide-specific CTL populations can differ between monkeys that share the same restricting major histocompatibility complex class I molecule and receive the same vaccine immunogens.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, Massachusetts 02215, USA.
authors.forename: Sandrine L
authors.initials: SL
authors.lastname: Hulot
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Pritha
authors.initials: P
authors.lastname: Sen
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Autissier
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Manuel
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D000939:Epitopes / Q000737:chemistry*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D000882:Haplorhini; D007107:Immune System; D008253:Macaca mulatta; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology*; D013997:Time Factors; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D054299:env Gene Products, Human Immunodeficiency Virus