Intramolecular immunodominance and intermolecular selection of H2^d-restricted peptides define the same immunodominant region of the measles virus fusion protein

The generation of a sustained antibody response requires the participation of MHC class II-restricted T helper cells. We have identified class II-restricted sequences by immunizing BALB/c (H-2^d) mice with 108 overlapping synthetic pentadecapeptides covering the whole sequence of the measles virus fusion protein (MV-F). Several strong T cell epitopes were found including a major cluster of H-2^d-restricted peptides between amino acids 256 and 305. Some of these peptides including peptide F(421-435) and F(256-270) induced MV-specific T lymphocytes in vivo while other H2^d-restricted MV-F sequences did not. Immunization with mixtures of selected peptides indicated a hierarchy among H2^d-restricted sequences due to competition between peptides. The dominant peptide F(421-435) impaired the response to other T cell epitopes including F(256-270). The response to F(91-105) was obliterated by F(421-435) and F(256-270) but not by peptides devoid of a T cell epitope. When BALB/c mice were immunized with the MV, the immunodominant sequence F(421-445) was identified which included the synthetic peptide F(421-435). Our data suggest that competition during processing and/or presentation between H2^d-restricted peptides defines the immunodominant sequence of the viral protein. Eventhough only a single immunodominant region was defined after immunization with the MV, peptides from other regions were able to induce MV-specific T cell responses. This finding is of interest for the design of subunit vaccines in general and for studying MV-specific T helper cells in an animal model in particular.