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Selected Publication:

Brooks, CL; Müller-Loennies, S; Brade, L; Kosma, P; Hirama, T; MacKenzie, CR; Brade, H; Evans, SV.
(2008): Exploration of specificity in germline monoclonal antibody recognition of a range of natural and synthetic epitopes.
J Mol Biol. 2008; 377(2):450-468 FullText FullText_BOKU

Abstract:
To explore the molecular basis of antigen recognition by germline antibodies, we have determined to high resolution the structures of the near-germline monoclonal antibody S25-2 in complex with seven distinct carbohydrate antigens based on the bacterial sugar 3-deoxy-alpha-D-manno-oct-2-ulosonic acid (Kdo). In contrast to previous findings, the inherited germline Kdo monosaccharide binding site is not restricted to this bacterial sugar but is able to accommodate an array of substitutions and chemical modifications of Kdo, including naturally occurring antigens containing the related monosaccharide D-glycero-alpha-D-talo-oct-2-ulosonic acid as well as nonterminal Kdo residues. However, we show by surface plasmon resonance and ELISA how antibody S25-2 specificity is so dependent on the context in which the antigen is presented that a free disaccharide displays strong binding while the same lipid-A-bound disaccharide does not bind. These structures provide insight into how inherited germline genes code for immunoglobulins of limited flexibility that are capable of binding a range of epitopes from which affinity-matured antibodies are generated. (C) 2008 Elsevier Ltd. All rights reserved.
Authors BOKU Wien:
Kosma Paul
BOKU Gendermonitor:

Find related publications in this database (using NML MeSH Indexing)
Animals -
Antibodies, Monoclonal - chemistry
Antibody Specificity -
Antigens - chemistry
Biological Products - chemistry
Chlamydophila psittaci - chemistry
Enzyme-Linked Immunosorbent Assay -
Epitopes - chemistry
Lipopolysaccharides - chemistry
Mice -
Models, Molecular -
Molecular Structure -
Protein Binding -
Protein Structure, Tertiary -
Sugar Acids - immunology
Surface Plasmon Resonance -

Find related publications in this database (Keywords)
protein crystallography
protein-carbohydrate interactions
antibody-antigen structure
antibody specificity
germline antibody


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