Murine Anti-vaccinia Virus D8 Antibodies Target Different Epitopes and Differ in Their Ability to Block D8 Binding to CS-E

PLoS Pathogens

Andrew B. Ward¹  Natalia de Val¹  Yan Xiang²  Xiangzhi Meng²  Andrew Schlossman³  Dirk M. Zajonc³  Michael H. Matho³  Bjoern Peters⁴  Shane Crotty⁴  Gregory M. Miller⁵  Linda C. Hsieh-Wilson⁵  Joshua Brown⁵ 

[1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, United States of America;Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, Texas, United States of America;Division of Cell Biology, La Jolla Institute for Allergy and Imunology (LIAI), La Jolla, California, United States of America;Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California, United States of America;Howard Hughes Medical Institute, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, United States of America

关键词: Sulfates;    Oligomers;    Microarrays;    Vaccinia virus;    Antibodies;    Alanine;    Chondroitin;    Negative staining;   

DOI  :  10.1371/journal.ppat.1004495

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY