CD4+ T-cell-epitope escape mutant virus selected in vivo.
Mutations in viral genomes that affect T-cell-receptor recognition by CD8+ cytotoxic T lymphocytes have been shown to allow viral evasion from immune surveillance during persistent viral infections. Although CD4+ T-helper cells are crucially involved in the maintenance of effective cytotoxic T-lymphocyte and neutralizing-antibody responses, their role in viral clearance and therefore in imposing similar selective pressures on the virus is unclear. We show here that transgenic virus-specific CD4+ Tcells, transferred into mice persistently infected with lymphocytic choriomeningitis virus, select for T-helper epitope mutant viruses that are not recognized. Together with the observed antigenic variation of the same T-helper epitope during polyclonal CD4+ T-cell responses in infected pore-forming protein-deficient C57BL/6 mice, this finding indicates that viral escape from CD4+ T lymphocytes is a possible mechanism of virus persistence.
Ciurea
A
A
Institute for Experimental Immunology, University Hospital, Zurich, Switzerland. adrian.ciurea@dim.usz.ch
Hunziker
L
L
Martinic
M M
MM
Oxenius
A
A
Hengartner
H
H
Zinkernagel
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D004247:DNA; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D008561:Membrane Fusion / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D012328:RNA Viruses / Q000502:physiology*
D000939:Epitopes; D004247:DNA