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 participa tion of MHC class II-restricted T helper cells. We have identified cla ss II-restricted sequences by immunizing BALB/c (H-2(d)) mice with 108 overlapping synthetic pentadecapeptides covering the whole sequence o f the measles virus fusion protein (MV-F). Several strong T cell epito pes were found including a major cluster of H-2(d)-restricted peptides between amino acids 256 and 305. Some of these peptides including pep tide F(421-435) and F(256-270) induced MV-specific T lymphocytes in vi vo while other H2(d)-restricted MV-F sequences did not. Immunization w ith mixtures of selected peptides indicated a hierarchy among H2(d)-re stricted sequences due to competition between peptides. The dominant p eptide F(421-435) impaired the response to other T cell epitopes inclu ding F(256-270). The response to F(91-105) was obliterated by F(421-43 5) 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(421-43 5). Our data suggest that competition during processing and/or present ation between H2(d)-restricted peptides defines the immunodominant seq uence of the viral protein. Eventhough only a single immunodominant re gion was defined after immunization with the MV, peptides from other r egions were able to induce MV-specific T cell responses. This finding is of interest for the design of subunit vaccines in general and for s tudying MV-specific T helper cells in an animal model in particular.