INTRAMOLECULAR IMMUNODOMINANCE AND INTERMOLECULAR SELECTION OF H2(D)-RESTRICTED PEPTIDES DEFINE THE SAME IMMUNODOMINANT REGION OF THE MEASLES-VIRUS FUSION PROTEIN
Cp. Muller et al., INTRAMOLECULAR IMMUNODOMINANCE AND INTERMOLECULAR SELECTION OF H2(D)-RESTRICTED PEPTIDES DEFINE THE SAME IMMUNODOMINANT REGION OF THE MEASLES-VIRUS FUSION PROTEIN, Molecular immunology, 32(1), 1995, pp. 37-47
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.