title: CD8 T-cell recognition of multiple epitopes within specific Gag regions is associated with maintenance of a low steady-state viremia in human immunodeficiency virus type 1-seropositive patients.
abstract: The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted. While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles. In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HLA class I alleles in a cohort of HIV-seropositive bar workers. Possession of the HLA class I alleles B5801, B8101, and B0702 was associated with a low median viral load and simultaneously with a broader median recognition of Gag epitopes compared to all other HLA alleles (twofold increase) (P = 0.0035). We further found an inverse linear relationship between the number of Gag epitopes recognized and the plasma viral load (R = -0.36; P = 0.0016). Particularly, recognition of multiple epitopes within two regions of Gag (amino acids [aa] 1 to 75 and aa 248 to 500) was associated with the maintenance of a low steady-state viremia, even years after acute infection.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases/NIH, Bethesda, MD 20892, USA. cgeldmacher@mmrp.org
authors.forename: Christof
authors.initials: C
authors.lastname: Geldmacher
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Currier
authors.forename: Eva
authors.initials: E
authors.lastname: Herrmann
authors.forename: Antelmo
authors.initials: A
authors.lastname: Haule
authors.forename: Ellen
authors.initials: E
authors.lastname: Kuta
authors.forename: Francine
authors.initials: F
authors.lastname: McCutchan
authors.forename: Lilian
authors.initials: L
authors.lastname: Njovu
authors.forename: Steffen
authors.initials: S
authors.lastname: Geis
authors.forename: Oliver
authors.initials: O
authors.lastname: Hoffmann
authors.forename: Leonard
authors.initials: L
authors.lastname: Maboko
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Deborah
authors.initials: D
authors.lastname: Birx
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.forename: Michael
authors.initials: M
authors.lastname: Hoelscher
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005805:Genes, MHC Class I; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication
chemical_list: D000939:Epitopes; D015683:Gene Products, gag