title: Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization.
abstract: Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope. Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays.
authors.affiliation: Department of Medicine, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Pathology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Bywaters
authors.affiliation: Department of Pathology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Brendle
authors.affiliation: Department of Medicine, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 USA.
authors.forename: Hyunwook
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Medicine, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ashley
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 5th Ave, Pittsburgh, PA 15260 USA.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Makhov
authors.affiliation: Department of Structural Biology, University of Pittsburgh School of Medicine, 3501 5th Ave, Pittsburgh, PA 15260 USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Conway
authors.affiliation: Department of Pathology, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 USA.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Christensen
authors.affiliation: Department of Medicine, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033 USA. Electronic address: shafenstein@hmc.psu.edu.
authors.forename: Susan
authors.initials: S
authors.lastname: Hafenstein
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology*; D000914:Antibodies, Viral / Q000737:chemistry* / Q000276:immunology*; D020285:Cryoelectron Microscopy; D018604:Epitope Mapping; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000648:ultrastructure*; D009500:Neutralization Tests; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
keywords: Conformation; Crosslinking; Cryo-EM; Epitope; HPV16; Human papillomavirus; Neutralization; Stabilization; Virus Fab complex; mAb