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Germline antibody recognition of distinct carbohydrate epitopes.

Nguyen HP, Seto NO, MacKenzie CR, Brade L, Kosma P, Brade H, Evans SV
Nat Struct Biol 10 1019-25 (2003)
Related entries: 1q9k, 1q9l, 1q9o, 3sy0, 3t4y, 3t65, 3t77

Cited: 76 times
EuropePMC logo PMID: 14625588

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 monosaccharide residue binding site with a subset of complementarity-determining regions (CDRs) of limited flexibility positioned to recognize the remainder of an array of different epitopes. This strategy allows germline antibodies to adapt to different epitopes while minimizing entropic penalties associated with the immobilization of labile CDRs upon binding of antigen, and provides insight into the link between the genetic origin of individual CDRs and their respective roles in antigen recognition.

Articles - 1q9w mentioned but not cited (3)

  1. Multi-constraint computational design suggests that native sequences of germline antibody H3 loops are nearly optimal for conformational flexibility. Babor M, Kortemme T. Proteins 75 846-858 (2009)
  2. Analysis of cross-reactive and specific anti-carbohydrate antibodies against lipopolysaccharide from Chlamydophila psittaci. Gerstenbruch S, Brooks CL, Kosma P, Brade L, Mackenzie CR, Evans SV, Brade H, Müller-Loennies S. Glycobiology 20 461-472 (2010)
  3. A complete, multi-level conformational clustering of antibody complementarity-determining regions. Nikoloudis D, Pitts JE, Saldanha JW. PeerJ 2 e456 (2014)


Reviews citing this publication (5)

  1. Antibody recognition of carbohydrate epitopes†. Haji-Ghassemi O, Blackler RJ, Martin Young N, Evans SV. Glycobiology 25 920-952 (2015)
  2. Glycan array: a powerful tool for glycomics studies. Liang CH, Wu CY. Expert Rev Proteomics 6 631-645 (2009)
  3. Breaking the law: unconventional strategies for antibody diversification. Kanyavuz A, Marey-Jarossay A, Lacroix-Desmazes S, Dimitrov JD. Nat Rev Immunol 19 355-368 (2019)
  4. The ABCs (Antibody, B cells, and Carbohydrate epitopes) of cholera immunity: considerations for an improved vaccine. Provenzano D, Kovác P, Wade WF. Microbiol Immunol 50 899-927 (2006)
  5. The History of Carbohydrates in Type I Allergy. Hils M, Wölbing F, Hilger C, Fischer J, Hoffard N, Biedermann T. Front Immunol 11 586924 (2020)

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