CTL escape and increased viremia irrespective of HIV-specific CD4+ T-helper responses in two HIV-infected individuals.
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.
Geels
Mark J
MJ
Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, The Netherlands. M.j.Geels@amc.uva.nl
Jansen
Christine A
CA
Baan
Elly
E
De Cuyper
Iris M
IM
van Schijndel
Gijs J M
GJ
Schuitemaker
Hanneke
H
Goudsmit
Jaap
J
Pollakis
Georgios
G
Miedema
Frank
F
Paxton
William A
WA
van Baarle
Debbie
D
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
D018984:Epitopes, T-Lymphocyte