T-Cell epitope mapping the PorB protein of serogroup B Neisseria meningitidis in B10 congenic strains of mice.
T-cell epitope mapping the meningococcal serotype 15 PorB protein performed in this study in three congenic strains of mice with B10 genetic background revealed at least three murine T-cell epitopes (55-72, 163-180, and 226-261), located in the highly conserved putative transmembrane regions of Neisserial porins. Proliferation assays with popliteal lymph node cells derived from mice immunized with the PorB protein or with synthetic 18-mer peptides showed that epitope 163-180 immunized only in the H-2d haplotype, epitope 55-72 could be presented by both H-2f and H-2s molecules, while the 226-261 region covered by three overlapping peptides could be efficiently recognized in context of all three MHC class II haplotypes studied. Inhibition experiments with blocking I-Aalpha- and I-Ealpha-specific mAb showed that peptide 163-180 was presented by I-Ad and peptide 244-261 was presented by both I-Af and I-As. In addition, evidence was obtained that peptide 226-243 was presented in context of H-2d or I-As haplotypes and peptide 55-72 was presented in context of I-Af and I-As loci. Finally, the Norwegian outer membrane vesicle vaccine, but not the purified PorB protein, could recall responses in mice immunized with synthetic peptides corresponding to the 226-261 region. Altogether, these results suggest that T-cell epitopes identified on the serotype 15 PorB protein, particularly those presented by several MHC class II molecules (e.g., 226-261), could have important implications for the development of meningococcal vaccines.
Delvig
A A
AA
The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, United Kingdom. alexei.delvig@ncl.ac.uk
Rosenqvist
E
E
Oftung
F
F
Robinson
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D018604:Epitope Mapping; D006239:Haplotypes; D007114:Immunization; D016056:Immunodominant Epitopes / Q000032:analysis; D007719:Knee Joint; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000145:classification; D018272:Porins; D012703:Serotyping; D013601:T-Lymphocytes / Q000276:immunology*
D001425:Bacterial Outer Membrane Proteins; D016056:Immunodominant Epitopes; D018272:Porins; C057699:porin protein, Neisseria