Peptide mimic of phosphorylcholine, a dominant epitope found on Streptococcus pneumoniae.
Identifieur interne : 002575 ( PubMed/Corpus ); précédent : 002574; suivant : 002576Peptide mimic of phosphorylcholine, a dominant epitope found on Streptococcus pneumoniae.
Auteurs : S L Harris ; M K Park ; M H Nahm ; B. DiamondSource :
- Infection and immunity [ 0019-9567 ] ; 2000.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Anti-Idiotypic (immunology), Antibodies, Monoclonal (metabolism), Cattle, Cross Reactions, Immunization, Immunodominant Epitopes (immunology), Immunoglobulin G (biosynthesis), Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Molecular Mimicry, Molecular Sequence Data, Opsonin Proteins, Peptides (chemistry), Peptides (immunology), Phosphorylcholine (chemistry), Phosphorylcholine (immunology), Phosphorylcholine (metabolism), Pneumococcal Infections (microbiology), Pneumococcal Infections (prevention & control), Serum Albumin, Bovine, Streptococcus pneumoniae (chemistry), Streptococcus pneumoniae (immunology), Vaccines, Conjugate.
- MESH :
- chemical , biosynthesis : Immunoglobulin G.
- chemical , chemistry : Peptides, Phosphorylcholine.
- chemical , immunology : Antibodies, Anti-Idiotypic, Immunodominant Epitopes, Peptides, Phosphorylcholine.
- chemical , metabolism : Antibodies, Monoclonal, Phosphorylcholine.
- chemistry : Streptococcus pneumoniae.
- immunology : Streptococcus pneumoniae.
- microbiology : Pneumococcal Infections.
- prevention & control : Pneumococcal Infections.
- Amino Acid Sequence, Animals, Cattle, Cross Reactions, Immunization, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Molecular Mimicry, Molecular Sequence Data, Opsonin Proteins, Serum Albumin, Bovine, Vaccines, Conjugate.
Abstract
Even in the age of antibiotics, Streptococcus pneumoniae causes significant morbidity, especially in the young, the elderly, and the immunocompromised. While a carbohydrate-based vaccine exists, it is poorly immunogenic in the at-risk populations. In mice, antibodies directed against phosphorylcholine (PC), an epitope present on the cell wall C polysaccharide of all pneumococcal serotypes, protect against infection. However, PC itself is a poor vaccine candidate. We report here peptide mimics of PC based on the anti-idiotypic interaction of T15 anti-PC antibodies. T15 antibodies, the dominant and protective idiotype induced in mice by PC immunization, self-associate via a 24-amino-acid region in the PC binding site (ASRNKANDYTTEYSASVKGRFIVS; peptide 1). Peptide 1 has been shown to bind in the PC binding site. We demonstrated that amino acid sequences derived from peptide 1 starting at amino acid 9, 11, or 13 inhibit PC binding. Therefore, we immunized mice with bovine serum albumin (BSA) conjugates of peptide 1 or either of two selected 12-mers. The 12-mer peptides were not immunogenic. Mice immunized with peptide 1-BSA developed an anti-PC response consisting mainly immunoglobulin G1 and expressed the T15 heavy chain. Nonetheless, neither BALB/c nor CBA/N mice were protected from lethal pneumococcal infections by immunization with peptide 1-BSA. Preliminary data suggest that peptide 1-BSA is not able to elicit the canonical T15 light chain, explaining the absence of protection. This idiotype-derived mimotope of PC is a useful tool for understanding immunologic cross-reactivity and learning to design T-cell-dependent vaccines for S. pneumoniae.
DOI: 10.1128/iai.68.10.5778-5784.2000
PubMed: 10992485
Links to Exploration step
pubmed:10992485Le document en format XML
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<front><div type="abstract" xml:lang="en">Even in the age of antibiotics, Streptococcus pneumoniae causes significant morbidity, especially in the young, the elderly, and the immunocompromised. While a carbohydrate-based vaccine exists, it is poorly immunogenic in the at-risk populations. In mice, antibodies directed against phosphorylcholine (PC), an epitope present on the cell wall C polysaccharide of all pneumococcal serotypes, protect against infection. However, PC itself is a poor vaccine candidate. We report here peptide mimics of PC based on the anti-idiotypic interaction of T15 anti-PC antibodies. T15 antibodies, the dominant and protective idiotype induced in mice by PC immunization, self-associate via a 24-amino-acid region in the PC binding site (ASRNKANDYTTEYSASVKGRFIVS; peptide 1). Peptide 1 has been shown to bind in the PC binding site. We demonstrated that amino acid sequences derived from peptide 1 starting at amino acid 9, 11, or 13 inhibit PC binding. Therefore, we immunized mice with bovine serum albumin (BSA) conjugates of peptide 1 or either of two selected 12-mers. The 12-mer peptides were not immunogenic. Mice immunized with peptide 1-BSA developed an anti-PC response consisting mainly immunoglobulin G1 and expressed the T15 heavy chain. Nonetheless, neither BALB/c nor CBA/N mice were protected from lethal pneumococcal infections by immunization with peptide 1-BSA. Preliminary data suggest that peptide 1-BSA is not able to elicit the canonical T15 light chain, explaining the absence of protection. This idiotype-derived mimotope of PC is a useful tool for understanding immunologic cross-reactivity and learning to design T-cell-dependent vaccines for S. pneumoniae.</div>
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<Abstract><AbstractText>Even in the age of antibiotics, Streptococcus pneumoniae causes significant morbidity, especially in the young, the elderly, and the immunocompromised. While a carbohydrate-based vaccine exists, it is poorly immunogenic in the at-risk populations. In mice, antibodies directed against phosphorylcholine (PC), an epitope present on the cell wall C polysaccharide of all pneumococcal serotypes, protect against infection. However, PC itself is a poor vaccine candidate. We report here peptide mimics of PC based on the anti-idiotypic interaction of T15 anti-PC antibodies. T15 antibodies, the dominant and protective idiotype induced in mice by PC immunization, self-associate via a 24-amino-acid region in the PC binding site (ASRNKANDYTTEYSASVKGRFIVS; peptide 1). Peptide 1 has been shown to bind in the PC binding site. We demonstrated that amino acid sequences derived from peptide 1 starting at amino acid 9, 11, or 13 inhibit PC binding. Therefore, we immunized mice with bovine serum albumin (BSA) conjugates of peptide 1 or either of two selected 12-mers. The 12-mer peptides were not immunogenic. Mice immunized with peptide 1-BSA developed an anti-PC response consisting mainly immunoglobulin G1 and expressed the T15 heavy chain. Nonetheless, neither BALB/c nor CBA/N mice were protected from lethal pneumococcal infections by immunization with peptide 1-BSA. Preliminary data suggest that peptide 1-BSA is not able to elicit the canonical T15 light chain, explaining the absence of protection. This idiotype-derived mimotope of PC is a useful tool for understanding immunologic cross-reactivity and learning to design T-cell-dependent vaccines for S. pneumoniae.</AbstractText>
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