Structure and specificity of lamprey monoclonal antibodies
Brantley R. Herrin*,{dagger},{ddagger},§, Matthew N. Alder*,{dagger},{ddagger},§, Kenneth H. Roux¶, Christina Sina||, Götz R. A. Ehrhardt*,{dagger},{ddagger},§, Jeremy A. Boydston{ddagger}, Charles L. Turnbough, Jr.{ddagger}, and Max D. Cooper*,{dagger},{ddagger},§,**
Departments of *Medicine, {dagger}Pediatrics, {ddagger}Microbiology, and §Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; ¶Department of Biological Science, Florida State University, Tallahassee, FL 32306; and ||University of Kiel, 24098 Kiel, Germany
Published online on January 31, 2008, 10.1073/pnas.0711619105 OPEN ACCESS ARTICLE
pnas.org
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 ß-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. |
