title: Variable lymphocyte receptor recognition of the immunodominant glycoprotein of Bacillus anthracis spores.
abstract: Variable lymphocyte receptors (VLRs) are the adaptive immune receptors of jawless fish, which evolved adaptive immunity independent of other vertebrates. In lieu of the immunoglobulin fold-based T and B cell receptors, lymphocyte-like cells of jawless fish express VLRs (VLRA, VLRB, or VLRC) composed of leucine-rich repeats and are similar to toll-like receptors (TLRs) in structure, but antibodies (VLRB) and T cell receptors (VLRA and VLRC) in function. Here, we present the structural and biochemical characterization of VLR4, a VLRB, in complex with BclA, the immunodominant glycoprotein of Bacillus anthracis spores. Using a combination of crystallography, mutagenesis, and binding studies, we delineate the mode of antigen recognition and binding between VLR4 and BclA, examine commonalities in VLRB recognition of antigens, and demonstrate the potential of VLR4 as a diagnostic tool for the identification of B. anthracis spores.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Kirchdoerfer
authors.forename: Brantley R
authors.initials: BR
authors.lastname: Herrin
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Han
authors.forename: Charles L
authors.initials: CL
authors.lastname: Turnbough
authors.forename: Max D
authors.initials: MD
authors.lastname: Cooper
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001408:Bacillus anthracis / Q000737:chemistry*; D003001:Cloning, Molecular; D003461:Crystallography; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000378:metabolism; D007798:Lampreys / Q000276:immunology*; D008958:Models, Molecular; D016296:Mutagenesis; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000737:chemistry*; D013171:Spores, Bacterial / Q000737:chemistry
chemical_list: D006023:Glycoproteins; D016056:Immunodominant Epitopes; D011971:Receptors, Immunologic