CTL escape and increased viremia irrespective of HIV-specific CD4+ T-helper responses in two HIV-infected individuals |
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Authors: | Geels Mark J Jansen Christine A Baan Elly De Cuyper Iris M van Schijndel Gijs J M Schuitemaker Hanneke Goudsmit Jaap Pollakis Georgios Miedema Frank Paxton William A van Baarle Debbie |
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Affiliation: | Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, The Netherlands. M.j.Geels@amc.uva.nl |
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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. |
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Keywords: | HIV Escape CTL CD4 CD8 Mutation |
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