The non-structural proteins of bluetongue virus are a dominant source of cytotoxic T cell peptide determinants.

Virus-specific, CD8+ cytotoxic T lymphocytes (CTLs) were generated in two strains of mice (BALB/c, CBA/Ca) against bluetongue virus serotype 10 (BTV-10). Recombinant vaccinia viruses (VV) expressing the individual structural and non-structural proteins of BTV were used to infect syngeneic target cells. We found that in both BALB/c (H-2d) and CBA/Ca (H-2k) mice, polyclonal CTL populations recognized target cells expressing the non-structural proteins better than those expressing the structural proteins. CTLs generated against other BTV serotypes also predominantly recognized the non-structural proteins. However, the extent of cross-reactivity was dependent on the H-2 background of the animals immunized. No CTLs cross-reactive to the BTV-10 heterotype were demonstrated with the panel of molecularly cloned recombinants in the H-2d haplotype. The outer capsid proteins VP2 and VP5 which vary considerably between serotypes were not recognized by heterotypic CTLs. Using this murine model we have determined which BTV proteins are the major targets of the CTL response. The implications for the design and development of subunit vaccines are discussed.