title: Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression.
abstract: CD8(+) T cells are a key focus of vaccine development efforts for HIV. However, there is no clear consensus as to which of the nine HIV proteins should be used for vaccination. The early proteins Tat, Rev, and Nef may be better CD8(+) T cell targets than the late-expressed structural proteins Gag, Pol, and Env. In this study, we show that Gag-specific CD8(+) T cells recognize infected CD4(+) T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation. Additionally, the number of Gag epitopes recognized by CD8(+) T cells was significantly associated with lower viremia (p = 0.0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag.
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711, USA.
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.forename: Chungwon
authors.initials: C
authors.lastname: Chung
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.forename: Sean P
authors.initials: SP
authors.lastname: Spencer
authors.forename: Anna K
authors.initials: AK
authors.lastname: Jonas
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Bean
authors.forename: Wonhee
authors.initials: W
authors.lastname: Lee
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Burwitz
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Stephany
authors.forename: John T
authors.initials: JT
authors.lastname: Loffredo
authors.forename: David B
authors.initials: DB
authors.lastname: Allison
authors.forename: Sama
authors.initials: S
authors.lastname: Adnan
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hoji
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Wilson
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013997:Time Factors; D016662:Virus Integration / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I