T-Helper Cell Epitopes on the E-Glycoprotein of Dengue 2 Jamaica Virus

To identify T-helper (T_h)-cell epitopes, we analyzed 25 synthetic peptides, which included most of the 495-amino-acid sequence of the envelope (E)-glycoprotein of dengue 2 virus. The peptides were analyzed in three mouse strains, BALB/c (H-2^d), C57BL/6 (H-2^b), and outbred NIH-Swiss, for their ability to elicit antibody or prime the T_h-cell compartment following two inoculations in Freund's incomplete adjuvant. Sixteen peptides were able to elicit an antipeptide antibody response in one or more mouse strain. Eleven antipeptide serum pools were able to bind to virus in ELISA. Fifteen peptides primed one or more haplotype for an in vitro antipeptide T_h-cell response as measured by blastogenesis. T_h-cell activation was generally confirmed by measurable in vitro production of intedeukin (IL)-2/IL-4. Nine peptides that were positive for in vitro blastogenesis, 1-2, 35, 4-6, 79, 142, 208, 06, 16, and 17, elicited virus-reactive T_h-cells in vitro in H-2^d mice. Two of these peptides (4-6 and 17) were able to prime virus-reactive T_h-cells in H-2^b mice. Nine peptides primed outbred mice in vivo for an antiviral antibody response significantly greater than that seen in animals primed with an irrelevant peptide. These results correlate with, and expand on, our previous observations based on a smaller set of synthetic peptides derived from the E-glycoprotein of Murray Valley encephalitis virus and suggest that synthetic peptides can function as E-glycoprotein T_h-cell epitopes. The similarity of results between two distantly related flaviviruses suggests that E-glycoprotein T_h-cell epitopes are consistent in location and activity.