Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences

Saputri, Dianita S.; Ismanto, Hendra S.; Nugraha, Dendi K.; Xu, Zichang; Horiguchi, Yasuhiko; Sakakibara, Shuhei; Standley, Daron M.; Cristea, Ileana M.

doi:https://doi.org/10.1128/msystems.00722-23

Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences

Saputri, Dianita S.; Ismanto, Hendra S.; Nugraha, Dendi K. et al.

mSystems, 2023, 8(6), e00722-23

アクセス数:540件（2025-08-20 14:19 集計）

固定URL: https://hdl.handle.net/11094/93389

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タイトル	Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences
著者	著者名 Saputri, Dianita S.
	著者名 Ismanto, Hendra S.
	NRID 1000000963430 1000000963430 ORCID 0000-0002-6995-5695 0000-0002-6995-5695 researchmap permalink dendikrisna dendikrisna 著者名 Nugraha, Dendi K.
	著者名 Xu, Zichang
	NRID 1000000183939 1000000183939 ORCID 0000-0002-1592-5861 0000-0002-1592-5861 researchmap permalink read0014308 read0014308 Scopus Author ID 7102798909 7102798909 著者名 Horiguchi, Yasuhiko
	NRID 1000010618838 1000010618838 著者名 Sakakibara, Shuhei
	NRID 1000000448028 1000000448028 researchmap permalink 7000011861 7000011861 著者名 Standley, Daron M.
	著者名 Cristea, Ileana M.
キーワード等	antibody
	antigen-specific
	B cell receptor
	clustering
	diphtheria
	pertussis
	tetanus
	repertoire
	SARS-CoV-2
	single-cell immune profile
内容	Saputri Dianita S., Ismanto Hendra S., Nugraha Dendi K., et al. Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences. mSystems 8, e00722-23 (2023); https://doi.org/10.1128/msystems.00722-23.
抄録	Recent advances in adaptive immune receptor repertoire sequencing have provided abundant B cell receptor (BCR) sequences under various conditions, including vaccination and disease. However, determining target antigen and epitope specificity of the corresponding antibodies is a major challenge due to their exceptional sequence diversity. Here, we introduce a novel method to cluster antibodies sharing antigenic targets based on their complementarity determining region (CDR) sequences. Using the proposed method, we demonstrate that SARS-CoV-2 spike protein receptor-binding domain (RBD) binders and non-RBD binders from publicly available BCR data were classified correctly, with a cluster purity of 95%. These clusters were then leveraged for annotating unlabeled COVID-19 patient BCR data, enabling the discovery of novel anti-RBD antibodies. We further validated the method by clustering BCR repertoires obtained from single-cell immune profiling of diphtheria-tetanus-pertussis (DTP)-vaccinated donors. Antibody expression and antigen-binding assays demonstrated that the clusters exhibited 96% antigen purity, surpassing the apparent 82% purity achieved by assigning antigens to the same B cells using fluorescently labeled DTP antigen probes. Moreover, antibodies within certain clusters were found to possess neutralizing activity, suggesting that CDR clusters contain epitope-level information. Together, this study offers a simple approach for antigen- and epitope-specific BCR discovery that is reproducible, inexpensive, and applicable to a wide range of antigen targets.
出版者	American Society for Microbiology
収録物名	mSystems
巻(号)	8(6)
ページ	e00722-23
刊行年月	2023-12-21
言語	英語
ハンドルURL	https://hdl.handle.net/11094/93389
eISSN	23795077
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1128/msystems.00722-23
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	mSystems. 2023, 8(6), p. e00722-23
DC.title	Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences
DC.creator	Saputri, Dianita S.
	Ismanto, Hendra S.
	Nugraha, Dendi K.
	Xu, Zichang
	Horiguchi, Yasuhiko
	Sakakibara, Shuhei
	Standley, Daron M.
	Cristea, Ileana M.
DC.publisher	American Society for Microbiology
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-12-21
DC.identifier	https://doi.org/10.1128/msystems.00722-23
DC.subject	antibody
	antigen-specific
	B cell receptor
	clustering
	diphtheria
	pertussis
	tetanus
	repertoire
	SARS-CoV-2
	single-cell immune profile
DC.description	Saputri Dianita S., Ismanto Hendra S., Nugraha Dendi K., et al. Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences. mSystems 8, e00722-23 (2023); https://doi.org/10.1128/msystems.00722-23.
DCTERMS.abstract	Recent advances in adaptive immune receptor repertoire sequencing have provided abundant B cell receptor (BCR) sequences under various conditions, including vaccination and disease. However, determining target antigen and epitope specificity of the corresponding antibodies is a major challenge due to their exceptional sequence diversity. Here, we introduce a novel method to cluster antibodies sharing antigenic targets based on their complementarity determining region (CDR) sequences. Using the proposed method, we demonstrate that SARS-CoV-2 spike protein receptor-binding domain (RBD) binders and non-RBD binders from publicly available BCR data were classified correctly, with a cluster purity of 95%. These clusters were then leveraged for annotating unlabeled COVID-19 patient BCR data, enabling the discovery of novel anti-RBD antibodies. We further validated the method by clustering BCR repertoires obtained from single-cell immune profiling of diphtheria-tetanus-pertussis (DTP)-vaccinated donors. Antibody expression and antigen-binding assays demonstrated that the clusters exhibited 96% antigen purity, surpassing the apparent 82% purity achieved by assigning antigens to the same B cells using fluorescently labeled DTP antigen probes. Moreover, antibodies within certain clusters were found to possess neutralizing activity, suggesting that CDR clusters contain epitope-level information. Together, this study offers a simple approach for antigen- and epitope-specific BCR discovery that is reproducible, inexpensive, and applicable to a wide range of antigen targets.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93389
citation_title	Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences
citation_author	Saputri, Dianita S.
	Ismanto, Hendra S.
	Nugraha, Dendi K.
	Xu, Zichang
	Horiguchi, Yasuhiko
	Sakakibara, Shuhei
	Standley, Daron M.
	Cristea, Ileana M.
citation_publisher	American Society for Microbiology
citation_language	英語
citation_date	2023-12-21
citation_journal_title	mSystems
citation_volume	8
citation_issue	6
citation_firstpage	e00722-23
citation_doi	https://doi.org/10.1128/msystems.00722-23
citation_public_url	https://hdl.handle.net/11094/93389

Deciphering the antigen specificities of antibodies by clustering their complementarity determining region sequences

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