Intramolecular immunodominance and intermolecular selection of H2d-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-2d) 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-2d-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 H2d-restricted MV-F sequences did not. Immunization with mixtures of selected peptides indicated a hierarchy among H2d-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 H2d-restricted peptides defines the immunodominant sequence of the viral protein. Even though 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.
Muller
C P
CP
Laboratoire National de Santé, Luxembourg.
Bünder
R
R
Mayser
H
H
Ammon
S
S
Weinmann
M
M
Brons
N H
NH
Schneider
F
F
Jung
G
G
Wiesmüller
K H
KH
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D002522:Chlorocebus aethiops; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D016056:Immunodominant Epitopes / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000276:immunology*
D000956:Antigens, Viral; D006183:H-2 Antigens; D016056:Immunodominant Epitopes; D014760:Viral Fusion Proteins