title: Structure and specificity of lamprey monoclonal antibodies.
abstract: Adaptive immunity in jawless vertebrates (lamprey and hagfish) is mediated by lymphocytes that undergo combinatorial assembly of leucine-rich repeat (LRR) gene segments to create a diverse repertoire of variable lymphocyte receptor (VLR) genes. Immunization with particulate antigens induces VLR-B-bearing lymphocytes to secrete antigen-specific VLR-B antibodies. Here, we describe the production of recombinant VLR-B antibodies specific for BclA, a major coat protein of Bacillus anthracis spores. The recombinant VLR-B antibodies possess 8-10 uniform subunits that collectively bind antigen with high avidity. Sequence analysis, mutagenesis, and modeling studies show that antigen binding involves residues in the beta-sheets lining the VLR-B concave surface. EM visualization reveals tetrameric and pentameric molecules having a central core and highly flexible pairs of stalk-region "arms" with antigen-binding "hands." Remarkable antigen-binding specificity, avidity, and stability predict that these unusual LRR-based monoclonal antibodies will find many biomedical uses.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Brantley R
authors.initials: BR
authors.lastname: Herrin
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Alder
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Roux
authors.forename: Christina
authors.initials: C
authors.lastname: Sina
authors.forename: Götz R A
authors.initials: GR
authors.lastname: Ehrhardt
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Boydston
authors.forename: Charles L
authors.initials: CL
authors.lastname: Turnbough
authors.forename: Max D
authors.initials: MD
authors.lastname: Cooper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology; D002460:Cell Line; D019281:Dimerization; D006801:Humans; D007798:Lampreys; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens