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• W2105388631 endingPage "864" @default.
• W2105388631 startingPage "853" @default.
• W2105388631 abstract "ABSTRACT Antibodies specific for capsular polysaccharides play a central role in immunity to encapsulated Streptococcus pneumoniae , but little is known about their genetics or the variable (V) region polymorphisms that affect their protective function. To begin to address these issues, we used combinatorial library cloning to isolate pneumococcal polysaccharide (PPS)-specific Fab fragments from two vaccinated adults. We determined complete V region primary structures and performed antigen binding analyses of seven Fab fragments specific for PPS serotype 6B, 14, or 23F. Fabs were of the immunoglobulin G2 or A isotype. Several V H III gene segments (HV 3-7, 3-15, 3-23, and 3-11) were identified. V L regions were encoded by several κ genes (KV 4-1, 3-15, 2-24, and 2D-29) and a λ gene (LV 1-51). Deviation of the V H and V L regions from their assigned germ line counterparts indicated that they were somatically mutated. Fabs of the same serotype specificity isolated from a single individual differed in affinity, and these differences could be accounted for either by the extent of mutation among clonal relatives or by usage of different V-region genes. Thus, functionally disparate anti-PPS antibodies can arise within individuals both by activation of independent clones and by intraclonal somatic mutation. For one pair of clonally related Fabs, the more extensively mutated V H was associated with lower affinity for PPS 14, a result suggesting that somatic mutation could lead to diminished protective efficacy. These findings indicate that the PPS repertoire in the adult derives from memory B-cell populations that have class switched and undergone extensive hypermutation." @default.
• W2105388631 created "2016-06-24" @default.
• W2105388631 creator A5023129638 @default.
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• W2105388631 creator A5060773083 @default.
• W2105388631 creator A5069699627 @default.
• W2105388631 date "2001-02-01" @default.
• W2105388631 modified "2023-10-17" @default.
• W2105388631 title "Combinatorial Library Cloning of Human Antibodies to<i>Streptococcus pneumoniae</i>Capsular Polysaccharides: Variable Region Primary Structures and Evidence for Somatic Mutation of Fab Fragments Specific for Capsular Serotypes 6B, 14, and 23F" @default.
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• W2105388631 doi "https://doi.org/10.1128/iai.69.2.853-864.2001" @default.
• W2105388631 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/97962" @default.
• W2105388631 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11159978" @default.
• W2105388631 hasPublicationYear "2001" @default.
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