Mapping and Characterization of the Primary and Anamnestic H-2 d -Restricted Cytotoxic T-Lymphocyte Response in Mice against Human Metapneumovirus

Abstract

ABSTRACT Cytotoxic T lymphocytes (CTLs) are important for the control of virus replication during respiratory infections. For human metapneumovirus (hMPV), an H-2 d -restricted CTL epitope in the M2-2 protein has been described. In this study, we screened the hMPV F, G, N, M, M2-1, and M2-2 proteins using three independent algorithms to predict H-2 d CTL epitopes in BALB/c mice. A dominant epitope (GYIDDNQSI) in positions 81 to 89 of the antitermination factor M2-1 and a subdominant epitope (SPKAGLLSL) in N 307-315 were detected during the anti-hMPV CTL response. Passive transfer of CD8 + T-cell lines against M2-1 81-89 and N 307-315 protected Rag1 −/− mice against hMPV challenge. Interestingly, diversification of CTL targets to include multiple epitopes was observed after repetitive infections. A subdominant response against the previously described M2-2 epitope was detected after the third infection. An understanding of the CTL response against hMPV is important for developing preventive and therapeutic strategies against the virus.