Clonal Analysis of the Cytotoxic T-Lymphocyte Response to Reovirus

Abstract

Reovirus has previously been classified into three serotypes based on hemagglutination inhibition assays. In the present study, the specificity of cytotoxic T lymphocytes (CTL) generated in reovirus type 3-infected C3H/HeN mice was investigated at the population and clonal levels. Short-term CTL lines generated in response to reovirus type 3 preferentially lysed cells infected with reovirus type 1 or 3 and, in some instances, type 2-infected cells as well. Eleven CTL clones established from the lines demonstrated two unique patterns of recognition. A single clone was exquisitely specific for reovirus type 3-infected cells and did not cross-react on reovirus type 1- or 2-infected cells. Ten of the clones recognized reovirus type 1- and type 3-infected cells. These clones had low levels of cross-reactivity on reovirus type 2-infected cells that was revealed only at high effector:target cell ratios. Precursor frequency analysis further revealed that the majority of the CTL generated against reovirus type 3 could cross-react on both reovirus type 1- and type 2-infected cells. Some CTL could be detected that had a more restricted pattern of recognition and recognized reovirus type 3-infected cells exclusively or recognized reovirus type 3-infected cells and either reovirus type 1- or type 2-infected cells. These results indicate that a minimum of four epitopes are recognized by reovirus-specific CTL and that the response is dominated by CTL that recognize an epitope common to all three serotypes of reovirus.