OBJECTIVES: Southwest Tanzania is affected by an HIV-1 epidemic consisting of subtypes A, C, and D, and their recombinant forms. This study was designed to assess whether the Gag- and Nef-specific T-cell response is biased towards recognizing the infecting subtype. METHODS: The infecting subtypes were characterized with a Multi-hybridization assay that discriminates between subtypes A, C and D. The interferon-gamma ELISPOT assay was used to detect the Gag- and Nef-specific T-cell responses in freshly isolated peripheral blood mononuclear cells in 56 seropositive patients. To study the HIV-specific T-cell responses, isolate-based Gag and Nef peptide sets representative of the locally occurring subtypes were used. The results were analysed at the total protein and single peptide level. RESULTS: In the study population, 35% were infected with a pure C subtype, 24% and 23% with ACD or AC recombinant forms, respectively. The total magnitude (P < 0.01) and breadth (P < 0.01) of the Gag-specific T-cell response detected with the subtype C-Gag peptide set was significantly greater than that detected with either the subtype A-Gag or D-Gag peptide sets. No significant difference was observed in the Nef-specific response. In 85% of responses targeting the most immunodominant Gag epitopes with subtype-specific sequence differences, the best recognized epitope variant corresponded to the infecting subtype. CONCLUSIONS: The Gag-specific T-cell response had a preference for recognizing peptides related to the infecting subtype.
OBJECTIVES: Southwest Tanzania is affected by an HIV-1 epidemic consisting of subtypes A, C, and D, and their recombinant forms. This study was designed to assess whether the Gag- and Nef-specific T-cell response is biased towards recognizing the infecting subtype. METHODS: The infecting subtypes were characterized with a Multi-hybridization assay that discriminates between subtypes A, C and D. The interferon-gamma ELISPOT assay was used to detect the Gag- and Nef-specific T-cell responses in freshly isolated peripheral blood mononuclear cells in 56 seropositive patients. To study the HIV-specific T-cell responses, isolate-based Gag and Nef peptide sets representative of the locally occurring subtypes were used. The results were analysed at the total protein and single peptide level. RESULTS: In the study population, 35% were infected with a pure C subtype, 24% and 23% with ACD or AC recombinant forms, respectively. The total magnitude (P < 0.01) and breadth (P < 0.01) of the Gag-specific T-cell response detected with the subtype C-Gag peptide set was significantly greater than that detected with either the subtype A-Gag or D-Gag peptide sets. No significant difference was observed in the Nef-specific response. In 85% of responses targeting the most immunodominant Gag epitopes with subtype-specific sequence differences, the best recognized epitope variant corresponded to the infecting subtype. CONCLUSIONS: The Gag-specific T-cell response had a preference for recognizing peptides related to the infecting subtype.
Authors: Christof Geldmacher; Ian S Metzler; Sodsai Tovanabutra; Tedi E Asher; Emma Gostick; David R Ambrozak; Constantinos Petrovas; Alexandra Schuetz; Njabulo Ngwenyama; Gustavo Kijak; Leonard Maboko; Michael Hoelscher; Francine McCutchan; David A Price; Daniel C Douek; Richard A Koup Journal: Blood Date: 2009-06-19 Impact factor: 22.113
Authors: Elmar Saathoff; Michael Pritsch; Christof Geldmacher; Oliver Hoffmann; Rebecca N Koehler; Leonard Maboko; Lucas Maganga; Steffen Geis; Francine E McCutchan; Gustavo H Kijak; Jerome H Kim; Miguel A Arroyo; Martina Gerhardt; Sodsai Tovanabutra; Merlin L Robb; Carolyn Williamson; Nelson L Michael; Michael Hoelscher Journal: J Acquir Immune Defic Syndr Date: 2010-07 Impact factor: 3.731
Authors: Jeffrey R Currier; Lynee M Galley; Holger Wenschuh; Vivian Morafo; Silvia Ratto-Kim; Clive M Gray; Leonard Maboko; Michael Hoelscher; Mary A Marovich; Josephine H Cox Journal: Clin Vaccine Immunol Date: 2007-12-12
Authors: Elena E Giorgi; Harikrishnan Balachandran; Mark Muldoon; Norman L Letvin; Barton F Haynes; Bette T Korber; Sampa Santra Journal: Vaccine Date: 2014-05-14 Impact factor: 3.641
Authors: Lyle R McKinnon; Xiaojuan Mao; Joshua Kimani; Charles Wachihi; Christina Semeniuk; Mark Mendoza; Binhua Liang; Ma Luo; Keith R Fowke; Francis A Plummer; T Blake Ball Journal: PLoS One Date: 2009-09-11 Impact factor: 3.240