Structure and specificity of lamprey monoclonal antibodies

Academic Article

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 β-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. © 2008 by The National Academy of Sciences of the USA.
  • Digital Object Identifier (doi)

    Author List

  • Herrin BR; Alder MN; Roux KH; Sina C; Ehrhardt GRA; Boydston JA; Turnbough CL; Cooper MD
  • Start Page

  • 2040
  • End Page

  • 2045
  • Volume

  • 105
  • Issue

  • 6