Peptide mimic of phosphorylcholine, a dominant epitope found on Streptococcus pneumoniae.
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.
Harris
S L
SL
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Park
M K
MK
Nahm
M H
MH
Diamond
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002417:Cattle; D003429:Cross Reactions; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009895:Opsonin Proteins; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D010767:Phosphorylcholine / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D011008:Pneumococcal Infections / Q000382:microbiology / Q000517:prevention & control; D012710:Serum Albumin, Bovine; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000276:immunology*; D018074:Vaccines, Conjugate
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D010455:Peptides; D018074:Vaccines, Conjugate; D010767:Phosphorylcholine; D012710:Serum Albumin, Bovine