title: Murine anti-vaccinia virus D8 antibodies target different epitopes and differ in their ability to block D8 binding to CS-E.
abstract: The IMV envelope protein D8 is an adhesion molecule and a major immunodominant antigen of vaccinia virus (VACV). Here we identified the optimal D8 ligand to be chondroitin sulfate E (CS-E). CS-E is characterized by a disaccharide moiety with two sulfated hydroxyl groups at positions 4' and 6' of GalNAc. To study the role of antibodies in preventing D8 adhesion to CS-E, we have used a panel of murine monoclonal antibodies, and tested their ability to compete with CS-E for D8 binding. Among four antibody specificity groups, MAbs of one group (group IV) fully abrogated CS-E binding, while MAbs of a second group (group III) displayed widely varying levels of CS-E blocking. Using EM, we identified the binding site for each antibody specificity group on D8. Recombinant D8 forms a hexameric arrangement, mediated by self-association of a small C-terminal domain of D8. We propose a model in which D8 oligomerization on the IMV would allow VACV to adhere to heterogeneous population of CS, including CS-C and potentially CS-A, while overall increasing binding efficiency to CS-E.
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Imunology (LIAI), La Jolla, California, United States of America.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Matho
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Natalia
authors.initials: N
authors.lastname: de Val
authors.affiliation: Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Miller
authors.affiliation: Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Joshua
authors.initials: J
authors.lastname: Brown
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Imunology (LIAI), La Jolla, California, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Schlossman
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Meng
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California, United States of America.
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California, United States of America.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Hsieh-Wilson
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Ward
authors.affiliation: Division of Cell Biology, La Jolla Institute for Allergy and Imunology (LIAI), La Jolla, California, United States of America.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Zajonc
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D014616:Vaccinia virus / Q000737:chemistry* / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins; D002809:Chondroitin Sulfates