Landscape of Non-canonical Cysteines in Human V H Repertoire Revealed by Immunogenetic Analysis.

Autor: Prabakaran P; Biologics Research, Sanofi, Framingham, MA 01701, USA. Electronic address: prabakaran.ponraj@sanofi.com., Chowdhury PS; Biologics Research, Sanofi, Framingham, MA 01701, USA. Electronic address: partha.chowdhury@sanofi.com.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2020 Jun 30; Vol. 31 (13), pp. 107831.
DOI: 10.1016/j.celrep.2020.107831
Abstrakt: Human antibody repertoire data captured through next-generation sequencing (NGS) has enabled deeper insights into B cell immunogenetics and paratope diversity. By analyzing large public NGS datasets, we map the landscape of non-canonical cysteines in human variable heavy-chain domains (V H s) at the repertoire level. We identify remarkable usage of non-canonical cysteines within the heavy-chain complementarity-determining region 3 (CDR-H3) and other CDRs and framework regions. Furthermore, our study reveals the diversity and location of non-canonical cysteines and their associated motifs in human V H s, which are reminiscent of and more complex than those found in other non-human species such as chicken, camel, llama, shark, and cow. These results explain how non-canonical cysteines strategically occur in the human antibodyome to expand its paratope space. This study will guide the design of human antibodies harboring disulfide-stabilized long CDR-H3s to access difficult-to-target epitopes and influence a paradigm shift in developability involving non-canonical cysteines.
Competing Interests: Declaration of Interests The authors are employees of Sanofi.
(Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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