2003
DOI: 10.1038/nsb1014
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Germline antibody recognition of distinct carbohydrate epitopes

Abstract: High-resolution structures reveal how a germline antibody can recognize a range of clinically relevant carbohydrate epitopes. The germline response to a carbohydrate immunogen can be critical to survivability, with selection for antibody gene segments that both confer protection against common pathogens and retain the flexibility to adapt to new disease organisms. We show here that antibody S25-2 binds several distinct inner-core epitopes of bacterial lipopolysaccharides (LPSs) by linking an inherited monosacc… Show more

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Cited by 106 publications
(130 citation statements)
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“…This raises the interesting possibility that the germline VH genes from which 4497 and 6078 developed may contain a paratope with baseline affinity for pyranose saccharides that serves as a handle for affinity maturation towards specific bacterial cell wall structures. A similar paradigm was identified for antibodies that recognize inner core sugars of LPS on the surface of pathogenic Chlamydia strains, 42 reinforcing the idea that a subset of germline VH gene segments may contain structural elements favorable for development of anti-polysaccharide antibodies.…”
Section: Discussionmentioning
confidence: 55%
“…This raises the interesting possibility that the germline VH genes from which 4497 and 6078 developed may contain a paratope with baseline affinity for pyranose saccharides that serves as a handle for affinity maturation towards specific bacterial cell wall structures. A similar paradigm was identified for antibodies that recognize inner core sugars of LPS on the surface of pathogenic Chlamydia strains, 42 reinforcing the idea that a subset of germline VH gene segments may contain structural elements favorable for development of anti-polysaccharide antibodies.…”
Section: Discussionmentioning
confidence: 55%
“…Our data illustrate the importance of paratope adaptability *Structural Biology Unit, National Institute of Immunology, New Delhi 110 067, India; and † Regional Centre for Biotechnology, Gurgaon 122 016, India for facilitating polyreactivity of germline mAb through systematically designed crystallographic experiments. The present analysis, in light of earlier studies (1,5,8,9,(14)(15)(16)(17)(18)(19), suggests the possibility that generation of diversity in the primary Ab repertoire may involve multiple mechanisms in a hierarchical order. The proposed model may account for enhanced diversity of primary immune receptors without increasing the size of the germline gene repertoire.…”
mentioning
confidence: 84%
“…It was suggested that a degree of polyreactivity within a germline Ab would provide a way by which a single Ab would be able to recognize a range of Ags and so obviate the requirement for a singular Ab for every potential non-self immunogen (5)(6)(7)(8)(9). Even the mutation-driven modulations of epitopes could be handled very efficiently by primary humoral immune defense through use of such polyreactive Abs (10).…”
mentioning
confidence: 99%
“…The structure was determined by molecular replacement using an unliganded germline mouse Fab Protein Data Bank (PDB identifier 1Q9 V) as the initial search model. 21 Because the four averaged molecules in the asymmetric unit were similar, only molecule 1 will be described here (Figure 1b). The 6A7 Fab-Bax peptide complex had good stereochemistry with only A151 from the light chain in the .…”
Section: Resultsmentioning
confidence: 99%
“…35,36 The search model was an unliganded mouse germline Fab ((PDB) identifier 1Q9V) with the loops connecting the constant and variable regions removed. 21 The initial model was improved with rigid body refinement using the program Crystallography & NMR System (CNS). 37 Multiple rounds of refinement with CNS and model building with O were used to improve the model when the peptide was added.…”
Section: Methodsmentioning
confidence: 99%