Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains

被引：107

作者：

Zhu, Jiang ^{[1
,7
,8
]}

Ofek, Gilad ^{[1
]}

Yang, Yongping ^{[1
]}

Zhang, Baoshan ^{[1
]}

Louder, Mark K. ^{[1
]}

Lu, Gabriel ^{[1
]}

McKee, Krisha ^{[1
]}

Pancera, Marie ^{[1
]}

Skinner, Jeff ^{[2
]}

Zhang, Zhenhai ^{[4
]}

Parks, Robert ^{[5
]}

Eudailey, Joshua ^{[5
]}

Lloyd, Krissey E. ^{[5
]}

Blinn, Julie ^{[5
]}

Alam, S. Munir ^{[5
]}

Haynes, Barton F. ^{[5
]}

Simek, Melissa ^{[6
]}

Burton, Dennis R. ^{[7
,8
,9
,10
]}

Koff, Wayne C. ^{[6
]}

Mullikin, James C. ^{[3
]}

Mascola, John R. ^{[1
]}

Shapiro, Lawrence ^{[1
,4
]}

Kwong, Peter D. ^{[1
]}

机构：

[1] NHGRI, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] NHGRI, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA

[3] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA

[4] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

[5] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA

[6] IAVI, New York, NY 10004 USA

[7] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[8] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[9] Massachusetts Gen Hosp, MIT, Ragon Inst, Cambridge, MA 02139 USA

[10] Harvard, Cambridge, MA 02139 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 16期

基金：

美国国家卫生研究院;

关键词：

antibody-affinity maturation; antibodyomics; B-cell ontogeny; DNA sequencing; immunological tolerance; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; HIV-1; BROAD; IDENTIFICATION; TECHNOLOGIES; INDIVIDUALS; CARDIOLIPIN; REPERTOIRE; SELECTION;

D O I：

10.1073/pnas.1219320110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Next-generation sequencing of antibody transcripts from HIV-1-infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and light-chain sequences from donor N152, the source of the broadly neutralizing antibody 10E8. We identified variants with up to 28% difference in amino acid sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants displayed similar architectures, and 10E8 variants reconstituted from matched and unmatched phylogenetic branches displayed significantly lower autoreactivity when matched. To test the generality of phylogenetic pairing, we analyzed donor International AIDS Vaccine Initiative 84, the source of antibodies PGT141-145. Heavy- and light-chain phylogenetic trees of PGT141-145 somatic variants also displayed remarkably similar architectures; in this case, branch pairings could be anchored by known PGT141-145 antibodies. Altogether, our findings suggest that phylogenetic matching of heavy and light chains can provide a means to approximate natural pairings.

引用

页码：6470 / 6475

页数：6

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