We have been investigating the T-helper (Th)-cell response to the flavivirus envelope (E)
glycoprotein. In our studies with
Murray Valley encephalitis (MVE) virus, we previously identified synthetic
peptides capable of priming Th lymphocytes for an in vitro antivirus proliferative response (J. H. Mathews, J. E. Allan, J. T. Roehrig, J. R. Brubaker, and A. R. Hunt, J. Virol. 65:5141-5148, 1991). We have now characterized in vivo Th-cell priming activity of one of these
peptides (MVE 17,
amino acids 356 to 376) and an analogous
peptide derived from the E-
glycoprotein sequence of the
dengue (DEN) 2, Jamaica strain (DEN 17,
amino acids 352 to 368). This DEN
peptide also primed the Th-cell compartment in BALB/c mice, as measured by in vitro proliferation and
interleukin production. The failure of some MVE and DEN virus synthetic
peptides to elicit an antibody response in BALB/c mice could be overcome if a Th-cell
epitope-containing
peptide was included in the immunization mixture. A more detailed analysis of the structural interactions between Th-cell and
B-cell epitope donor
peptides revealed that the
peptides must be linked to observe the enhanced antibody response. Blockage or deletion of the free
cysteine residue on either
peptide abrogated the antibody response. The most efficient T-
B-cell epitope interaction occurred when the
peptides were colinearly synthesized. These Th-cell-stimulating
peptides were also functional with the heterologous
B-cell epitope-containing
peptides. The Th-cell
epitope on DEN 17 was more potent than the Th-cell
epitope on MVE 17.