+Search query
-Structure paper
Title | Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses. |
---|---|
Journal, issue, pages | Sci Immunol, Vol. 6, Issue 66, Page eabl5842, Year 2021 |
Publish date | Dec 10, 2021 |
Authors | Jared Feldman / Julia Bals / Clara G Altomare / Kerri St Denis / Evan C Lam / Blake M Hauser / Larance Ronsard / Maya Sangesland / Thalia Bracamonte Moreno / Vintus Okonkwo / Nathania Hartojo / Alejandro B Balazs / Goran Bajic / Daniel Lingwood / Aaron G Schmidt / |
PubMed Abstract | Initial exposure to a pathogen elicits an adaptive immune response to control and eradicate the threat. Interrogating the abundance and specificity of the naive B cell repertoire drives understanding ...Initial exposure to a pathogen elicits an adaptive immune response to control and eradicate the threat. Interrogating the abundance and specificity of the naive B cell repertoire drives understanding of how to mount protective responses. Here, we isolated naive B cells from eight seronegative human donors targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD). Single-cell B cell receptor (BCR) sequencing identified diverse gene usage and no restriction on complementarity determining region length. A subset of recombinant antibodies produced by naive B cell precursors bound to SARS-CoV-2 RBD and engaged circulating variants including B.1.1.7, B.1.351, and B.1.617.2, as well as preemergent bat-derived coronaviruses RaTG13, SHC104, and WIV1. By structural characterization of a naive antibody in complex with SARS-CoV-2 spike, we identified a conserved mode of recognition shared with infection-induced antibodies. We found that representative naive antibodies could signal in a B cell activation assay, and by using directed evolution, we could select for a higher-affinity RBD interaction, conferred by a single amino acid change. The minimally mutated, affinity-matured antibodies also potently neutralized SARS-CoV-2. Understanding the SARS-CoV-2 RBD–specific naive repertoire may inform potential responses capable of recognizing future SARS-CoV-2 variants or emerging coronaviruses, enabling the development of pan-coronavirus vaccines aimed at engaging protective germline responses. |
External links | Sci Immunol / PubMed:34648356 / PubMed Central |
Methods | EM (single particle) |
Resolution | 8.6 Å |
Structure data | EMDB-24279: |
Source |
|