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Variable sequences in a mosaic-like domain of meningococcal tbp2 encode immunoreactive epitopes
B Rokbi1, G Maitre-Wilmotte, V Mazarin
1Pasteur Merieux Sérums and Vaccins, Marcy l'Etoile, France.
Abstract:
Transferrin-binding proteins from Neisseria meningitidis vary among different isolates. We have identified and studied a hypervariable region adjacent to the carboxyl-end of the transferrin-binding domain of the Tbp2 molecule. The tbp2 genes from six strains of N. meningitidis were cloned and sequenced in this particular region. Sequence analysis of these regions along with five other sequences available from pathogenic Neisseria showed a common organisation of seven highly variable nucleotide stretches interspersed with six conserved nucleotide stretches. The variable regions correlated with the location of immunoreactive epitopes in polyclonal antisera raised to transferrin-binding proteins identified by peptide pin technology. Sequence analysis suggested a mosaic-like organisation of the tbp2 genes. Taken together, these data suggest that the antigenic variation in this part of the protein may result from a strong host immune pressure.
Insights
Neisseria meningitidis transferrin-binding proteins (Tbp2) show variation due to a hypervariable region in the tbp2 gene. This variation likely results from host immune pressure, influencing antigenic epitopes.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Neisseria meningitidis utilizes transferrin-binding proteins (Tbp) for iron acquisition, crucial for pathogenesis.
- Variability in Tbp expression and structure among N. meningitidis isolates is recognized.
Purpose of the Study:
- To investigate the genetic basis of antigenic variation in the Tbp2 molecule of Neisseria meningitidis.
- To characterize a hypervariable region within the tbp2 gene and its relationship to immunoreactive epitopes.
Main Methods:
- Cloning and sequencing of the tbp2 gene from six N. meningitidis strains, focusing on a specific hypervariable region.
- Sequence analysis of identified regions alongside existing pathogenic Neisseria sequences.
- Correlation of sequence variability with immunoreactive epitopes using peptide pin technology and polyclonal antisera.
Main Results:
- Identification of a common organization in the tbp2 hypervariable region, consisting of seven variable and six conserved nucleotide stretches.
- Sequence analysis suggested a mosaic-like structure of the tbp2 genes.
- Variable regions directly corresponded to the location of immunoreactive epitopes.
Conclusions:
- The hypervariable region of the Tbp2 molecule in Neisseria meningitidis exhibits significant sequence diversity.
- Antigenic variation in this region is likely driven by host immune selection pressure.
- The mosaic-like organization of tbp2 genes contributes to immune evasion strategies of N. meningitidis.