title: Structural insights into parallel strategies for germline antibody recognition of lipopolysaccharide from Chlamydia.
abstract: The structure of the antigen-binding fragment from the monoclonal antibody S64-4 in complex with a pentasaccharide bisphosphate fragment from chlamydial lipopolysaccharide has been determined by x-ray diffraction to 2.6 Å resolution. Like the well-characterized antibody S25-2, S64-4 displays a pocket formed by the residues of germline sequence corresponding to the heavy and light chain V gene segments that binds the terminal Kdo residue of the antigen; however, although S64-4 shares the same heavy chain V gene segment as S25-2, it has a different light chain V gene segment. The new light chain V gene segment codes for a combining site that displays greater affinity, different specificity, and allows a novel antigen conformation that brings a greater number of antigen residues into the combining site than possible in S25-2. Further, while antibodies in the S25-2 family use complementarity determining region (CDR) H3 to discriminate among antigens, S64-4 achieves its specificity via the new light chain V gene segment and resulting change in antigen conformation. These structures reveal an intriguing parallel strategy where two different combinations of germline-coded V gene segments can act as starting points for the generation of germline antibodies against chlamydial antigens and show how anti-carbohydrate antibodies can exploit the conformational flexibility of this class of antigens to achieve high affinity and specificity independently of CDR H3.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, PO Box 3055 STN CSC, Victoria, BC, Canada V8P 3P6.
authors.forename: Dylan W
authors.initials: DW
authors.lastname: Evans
authors.forename: Sven
authors.initials: S
authors.lastname: Müller-Loennies
authors.forename: Cory L
authors.initials: CL
authors.lastname: Brooks
authors.forename: Lore
authors.initials: L
authors.lastname: Brade
authors.forename: Paul
authors.initials: P
authors.lastname: Kosma
authors.forename: Helmut
authors.initials: H
authors.lastname: Brade
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Evans
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D002236:Carbohydrate Conformation; D002689:Chlamydia / Q000737:chemistry* / Q000276:immunology; D018360:Crystallography, X-Ray; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D008070:Lipopolysaccharides