The L Antigen of the LCM Virus is a Target of Dominant CD8+ Responses (43.47)

Abstract

CD8+ T cell responses control lymphocytic choriomeningitis virus (LCMV) infection in H-2b mice. Although antigen-specific responses against LCMV infection are well studied, we found that up to one third of the CD8+CD44hi response to LCMV in H-2b mice was not accounted for by known epitopes. We screened peptides predicted to bind MHC Class I, and overlapping 15-mer peptides spanning the complete LCMV proteome for their capacity to induce interferon-γ (IFNγ) production from CD8+ T cells derived from LCMV-infected H-2b mice. We identified thirteen novel epitopes. These together with the 7 previously known epitopes account for the total CD8+CD44hi response, diminishing the possible role for bystander T cell activation. Strikingly, 9 out of the 13 new epitopes were derived from the viral L polymerase, which, until now, was not recognized as a target of the cellular response induced by LCMV infection. The L epitopes induced significant levels of in vivo cytotoxicity and conferred protection against LCMV challenge. Interestingly, protection from viral challenge was best correlated with the cytolytic potential of CD8+ T cells, whereas IFNγ production and peptide avidity appear to play a lesser role. Taken together, these findings illustrate that the LCMV-specific CD8+T cell response is more complex than previously appreciated.