8W0Y

Crystal structure of broadly neutralizing antibody hcab17 in complex with Hepatitis C virus envelope glycoprotein E2 ectodomain

Summary for 8W0Y

• Entry DOI: 10.2210/pdb8w0y/pdb
• Descriptor: hcab17 Fab Heavy Chain, hcab17 Fab Light Chain, Envelope glycoprotein E2, ... (8 entities in total)
• Functional Keywords: hcv glycoprotein, broadly neutralizing antibodies, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 160387.11

Authors

Flyak, A.I.,Wilcox, X.E. (deposition date: 2024-02-14, release date: 2024-03-27, Last modification date: 2024-11-06)

Primary citation

Ogega, C.O.,Skinner, N.E.,Schoenle, M.V.,Wilcox, X.E.,Frumento, N.,Wright, D.A.,Paul, H.T.,Sinnis-Bourozikas, A.,Clark, K.E.,Figueroa, A.,Bjorkman, P.J.,Ray, S.C.,Flyak, A.I.,Bailey, J.R.
Convergent evolution and targeting of diverse E2 epitopes by human broadly neutralizing antibodies are associated with HCV clearance.
Immunity, 57:890-903.e6, 2024

PubMed Abstract: The early appearance of broadly neutralizing antibodies (bNAbs) in serum is associated with spontaneous hepatitis C virus (HCV) clearance, but to date, the majority of bNAbs have been isolated from chronically infected donors. Most of these bNAbs use the V1-69 gene segment and target the envelope glycoprotein E2 front layer. Here, we performed longitudinal B cell receptor (BCR) repertoire analysis on an elite neutralizer who spontaneously cleared multiple HCV infections. We isolated 10,680 E2-reactive B cells, performed BCR sequencing, characterized monoclonal B cell cultures, and isolated bNAbs. In contrast to what has been seen in chronically infected donors, the bNAbs used a variety of V genes and targeted at least three distinct E2 antigenic sites, including sites previously thought to be non-neutralizing. Diverse front-layer-reactive bNAb lineages evolved convergently, acquiring breadth-enhancing somatic mutations. These findings demonstrate that HCV clearance-associated bNAbs are genetically diverse and bind distinct antigenic sites that should be the target of vaccine-induced bNAbs.

PubMed: 38518779
DOI: 10.1016/j.immuni.2024.03.001

Experimental method

X-RAY DIFFRACTION (3.31 Å)