THE NONSTRUCTURAL PROTEINS OF BLUETONGUE VIRUS ARE A DOMINANT SOURCE OF CYTOTOXIC T-CELL PEPTIDE DETERMINANTS

Virus-specific, CD8(+) cytotoxic T lymphocytes (CTLs) were generated i n two strains of mice (BALB/c, CBA/Ca) against bluetongue virus seroty pe 10 (BTV-10), Recombinant vaccinia viruses (VV) expressing the indiv idual structural and non-structural proteins of BTV were used to infec t syngeneic target cells. We found that in both BALB/c (H-2(d)) and CB A/Ca (H-2(k)) mice, polyclonal CTL populations recognized target cells expressing the non-structural proteins better than those expressing t he structural proteins. CTLs generated against other BTV serotypes als o predominantly recognized the non-structural proteins. However, the e xtent of cross-reactivity was dependent on the H-2 background of the a nimals immunized. No CTLs cross-reactive to the BTV-10 heterotype were demonstrated with the panel of molecularly cloned recombinants in the H-2(d) haplotype. The outer capsid proteins VP2 and VP5 which vary co nsiderably 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.