The target
epitopes, serotype specificity, and cytolytic function of dengue virus-specific T cells may influence their theoretical roles in protection against
secondary infection as well as the immunopathogenesis of
dengue hemorrhagic fever. To study these factors in an experimental system, we isolated dengue virus-specific CD4+ and CD8+ T-cell clones from dengue-2 virus-immunized BALB/c mice. The T-cell response to dengue virus in this mouse strain was heterogeneous; we identified at least five different CD4+ phenotypes and six different CD8+ phenotypes. Individual T-cell clones recognized
epitopes on the dengue virus pre-M, E, NSl/NS2A, and NS3
proteins and were restricted by the I-Ad, I-Ed, Ld, and Kd
antigens. Both serotype-specific and serotype-cross-reactive clones were isolated in the CD4+ and CD8+ subsets; among CD8+ clones, those that recognized the dengue virus structural
proteins were serotype specific whereas those that recognized the nonstructural
proteins were serotype cross-reactive. All of the CD8+ and one of five CD4+ clones lysed dengue virus-infected target cells. Using synthetic
peptides, we identified an Ld-restricted
epitope on the E
protein (residues 331 to 339, SPCKIPFEI) and a Kd-restricted
epitope on the NS3
protein (residues 296 to 310, ARGYISTRVEM GEAA). These data parallel previous findings of studies using human dengue virus-specific T-cell clones. This experimental mouse system may be useful for studying the role of the virus serotype and HLA haplotype on T-cell responses after primary dengue virus
infection.