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

Takehisa Chuma^2,

Trevor Williams^1,

¹ Institute of Virology & Environmental Microbiology, Mansfield Road, Oxford OX1 3SR, UK,
² Department of Public Health Services, University of Alabama at Birmingham, Birmingham, Alabama 3529, USA
and³ Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, OX1 3QU, UK

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-2^d) and CBA/Ca (H-2^k) 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-2^d 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.

^* Author for correspondence. Fax +44 1865 59962. e-mail por@mail.nerc-oxford.ac.uk

Present address: Laboratory of Veterinary Public Health, Department of Veterinary Medicine, Faculty of Agriculture, Kagoshima University, Kagoshima 890, Japan.

Present address: Ecosur, Aptdo Postal 36, Tapachula 30700 Chiapas, Mexico.

Received 11 July 1995; accepted 14 December 1995.