Uncovering subdominant cytotoxic T-lymphocyte responses in lymphocytic choriomeningitis virus-infected BALB/c mice

The cytotoxic T-lymphocyte response against lymphocytic choriomeningitis virus (LCMV) in BALB/c mice is predominantly directed against a single, L-d-restricted epitope in the viral nucleoprotein (residues 118 to 126), To investigate whether any K-d/D-d-restricted responses were activated but did not expand during the primary response, me used a BALB/c mutant, BALB/c-H-2(dm2), which does not express the Ld molecule. Splenocytes from LCMC-infected BALB/c mice were transferred into irradiated BALB/c-H-2(dm2) mice and rechallenged with LCMV. Thus, they were exposed to an antigenic stimulus without the involvement of the immunodominant L-d-restricted epitope. In this adoptive transfer model, the donor splenocytes protected the recipient mice against chronic LCMV infection by mounting a potent K-d- and/or D-d restricted secondary antiviral response. Analysis of a panel of ha binding LCMV peptides revealed that residues 283 to 291 from the viral glycoprotein (GP(283-291)) comprise a major new epitope in the adoptive transfer model, Because the donor splenocytes were first activated during the primary infection in BALB/c mice, the GP(283-291) epitope is a subdominant epitope in BALB/c mice that becomes dominant after rechallenge in BALB/c-H-2(dm2) mice, This study makes two points. First, it shows that subdominant CTL responses can be protective, and second, it provides a general experimental approach for uncovering subdominant CTL responses in vivo, This strategy can be used to identify subdominant T-cell responses in other systems.