EFFICIENT PRIMING OF CD8(-CELLS SPECIFIC FOR A SUBDOMINANT EPITOPE FOLLOWING SENDAI VIRUS-INFECTION() MEMORY T)

The relationship between the primary effector CTL response to viral in fection and the subsequent pool of memory CTL precursors (CTLp) is poo rly understood, Here, we have analyzed the induction of both effector CTL and memory CTLp to dominant and subdominant epitopes following Sen dai virus infection of C57BL/6 mice, A single peptide derived from the Sendai virus nucleoprotein (NP324-332) binds to both H-2 K-b and D-b MHC class molecules, generating both immunodominant (NP324-332/K-b) an d subdominant (NP324-332/D-b) epitopes, Following intranasal Sendai vi rus infection, NP324-332/K-b-specific CTL dominated the primary effect or CTL response in the lung and were present at high frequency in the memory CTLp pool, In contrast, NP324-332/D-b-specific CTL were not a d etectable component of the effector response to primary Sendai virus i nfection, However, memory CTLp specific for this subdominant epitope w ere induced at frequencies approaching those of CTLp specific for the immunodominant epitope, These data indicate that memory CTLp specific for subdominant epitopes can be primed by Sendai virus infection in th e absence of a detectable effector response, To determine whether CTLp memory to subdominant epitopes is functional in the context of Sendai virus infection, memory CTLp specific for a subdominant epitope were selectively primed by vaccination, These cells dominated the subsequen t effector CTL response to Sendai virus infection, demonstrating that memory CTLp primed against subdominant epitopes can participate in an immune response and effectively compete with T cells specific for immu nodominant epitopes, These data have implications for the development of vaccines designed to emphasize cellular immunity.