title: CTL escape and increased viremia irrespective of HIV-specific CD4+ T-helper responses in two HIV-infected individuals.
abstract: We investigated whether development of mutations leads to loss of CD8 T-cell recognition in HIV-1 infection and is possibly linked to alterations in HIV-1-specific CD4(+) T-cell responses in 2 HIV-infected individuals. In patient, H434 full genome sequencing of HIV-1 biological clones at early and late time points during disease progression showed development of fixed mutations in 16 predicted HIV-specific CTL epitopes. Loss of T-cell recognition and reactivity against wild-type and mutant epitopes was observed primarily for the HLA-B27-restricted KK10 epitope and HLA-A2-restricted SL9 epitope. Similarly, in patient H671, decreasing numbers of HLA-A3-restricted CD8(+) T cells specific for the wild-type RK9 epitope was observed after CTL escape. Only in patient H434 loss of CTL responses was paralleled by a decrease in HIV-specific IL-2(+) CD4(+) T-helper responses. This suggests that loss of T-cell reactivity may not be directly linked to HIV-specific CD4(+) T-cell responses but that increased viremia after CTL escape may influence CD4(+) T-helper responses.
authors.affiliation: Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, The Netherlands. M.j.Geels@amc.uva.nl
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Geels
authors.forename: Christine A
authors.initials: CA
authors.lastname: Jansen
authors.forename: Elly
authors.initials: E
authors.lastname: Baan
authors.forename: Iris M
authors.initials: IM
authors.lastname: De Cuyper
authors.forename: Gijs J M
authors.initials: GJ
authors.lastname: van Schijndel
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: Georgios
authors.initials: G
authors.lastname: Pollakis
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: William A
authors.initials: WA
authors.lastname: Paxton
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D016679:Genome, Viral; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D018655:Lymphocyte Count; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014766:Viremia
chemical_list: D018984:Epitopes, T-Lymphocyte