CD8+ cytotoxic T lymphocytes are key effectors of adaptive immunity for the control of virus infections. Epitope-specific responses are hierarchical and the rules for dominance are not well defined. Here we show that the H2-Kd-restricted RSV M2(82-90) (KdM2(82-90)) epitope dominates the H2-Db-restricted RSV M187-195 (DbM187-195) epitope and influences epitope-specific effector function in the acute and memory phases of the immune response to primary RSV infection in H-2b/d hybrid mice. The hybrid mouse model provides a system to define rules of epitope hierarchy and better understand how antigen presentation and epitope competition affect the phenotype of effector and memory T cells.