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 immun e surveillance during persistent viral infections. Although CD4(+) T-helper cells are crucially involved in the maintenance of effective cytotoxic T-l ymphocyte and neutralizing-antibody responses, their role in viral clearanc e and therefore in imposing similar selective pressures on the virus is unc lear. We show here that transgenic virus-specific CD4(+) T cells, transferr ed into mice persistently infected with lymphocytic choriomeningitis virus, select for T-helper epitope mutant viruses that are not recognized. Togeth er with the observed antigenic variation of the same T-helper epitope durin g polyclonal CD4(+) T-cell responses in infected pore-forming protein-defic ient C57BL/6 mice, this finding indicates that viral escape from CD4(+) T l ymphocytes is a possible mechanism of virus persistence.