Highly Reduced Protection against Streptococcus pneumoniae after Deletion of a Single Heavy Chain Gene in Mouse

Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae (SPn). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection. The abi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-05, Vol.97 (11), p.6031-6036
Main Authors: Mi, Qing-Sheng, Zhou, Li, Schulze, Dan H., Fischer, Randy T., Lustig, Ana, Rezanka, Louis J., Donovan, David M., Longo, Dan L., Kenny, James J.
Format: Article
Language:English
Subjects:
Alleles
Animals
Antibodies, Bacterial - biosynthesis
Antibodies, Bacterial - genetics
Antibodies, Bacterial - immunology
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - immunology
Antigens, Bacterial - immunology
AV1 gene
B lymphocytes
Bacteria
Bacterial Vaccines - immunology
Biological Sciences
Cross Reactions
DNA probes
Epitopes
Gene Deletion
Genes
Genes, Immunoglobulin
Genomics
Hemocyanins - immunology
Hybridomas
Hybridomas - immunology
Immunity, Innate - genetics
Immunization
Immunodominant Epitopes - immunology
Immunoglobulin Heavy Chains - genetics
Immunology
Infections
Mice
Mice, Knockout
Phosphocholine
Phosphorylcholine - immunology
Streptococcus pneumoniae
Streptococcus pneumoniae - immunology
V1 gene
Vaccination
Virulence
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Summary:Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae (SPn). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection. The ability of anti-PC Abs using H chains other than the V1 H chain to protect against pneumococcal infection remains controversial. We generated V1-/-knockout mice to determine whether protective anti-PC Abs could be produced in the absence of the V1 gene. No anti-PC Abs were produced in V1-/-mice immunized with avirulent SPn; however, PC-BSA binding Abs were induced after immunization with PC-keyhole limpet hemocyanin but at significantly lower levels than those in wild-type mice. These Abs provided poor protection against virulent SPn; thus,
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.110039497