Peptide mimotopes of pneumococcal capsular polysaccharide of 6B serotype: a peptide mimotope can bind to two unrelated antibodies.
Two groups of bacteriophage clones displaying the antigenic properties of serotype 6B pneumococcal capsular polysaccharide (PS) were obtained from different phage libraries expressing random heptameric peptides. One group, biopanned with a mouse mAb (Hyp6BM1), is comprised of 17 phage clones expressing 10 unique sequences of linear peptides. The other group, selected with another mAb (Hyp6BM8), contained six clones, all of which expressed the identical circular peptide. Phage clones expressing the linear peptides (e.g., PhaM1L3) bound only to Hyp6BM1, but not other 6B PS-specific mAb, and their binding could be inhibited with pneumococcal capsular type 6B PS only. In contrast, a phage clone expressing the circular peptide (PhaM8C1) cross-reacted with several other 6B PS-specific mAbs, and their binding could be inhibited with pneumococcal capsular PS of 6A and 6B serotypes. Two short peptides, PepM1L3 and PepM8C1, reflecting the peptide inserts of the corresponding phage clones, could inhibit the binding of the two clones to their respective mAb. Interestingly, the peptide insert in PhaM8C1 was identical to that in PhaB3C4, a previously reported mimotope of alpha(2-->8) polysialic acid, Neisseria meningitidis group B PS. Indeed, PhaM8C1 bound to HmenB3 (a meningococcal Ab), and their association could be inhibited with alpha(2-8) polysialic acid, but not with 6B PS. Conversely, alpha(2-8) polysialic acid could not inhibit the binding of PhaM8C1 to Hyp6BM8. The two-dimensional nuclear magnetic resonance studies indicate that PepM8C1 peptide can assume several conformations in solution. The ability of this peptide to assume multiple conformations might account for its ability to mimic more than one Ag type.
Shin
Jeon-Soo
JS
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
Yu
Jigui
J
Lin
Jisheng
J
Zhong
Linghao
L
Bren
Kara L
KL
Nahm
Moon H
MH
D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D017104:Bacteriophage M13 / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D001666:Binding Sites, Antibody; D003001:Cloning, Molecular; D003429:Cross Reactions; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D020539:Sequence Analysis, Protein; D013296:Streptococcus pneumoniae / Q000276:immunology*
D001426:Bacterial Proteins; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D011135:Polysaccharides, Bacterial; C437065:pneumococcal polysaccharide type 6