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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhu, J; Ofek, G; Yang, Y; Zhang, B; Louder, MK; Lu, G; McKee, K; Pancera, M; Skinner, J; Zhang, Z; Parks, R; Eudailey, J; Lloyd, KE; Blinn, J; Alam, SM; Haynes, BF; Simek, M; Burton, DR; Koff, WC; NISC Comparative Sequencing Program, ; Mullikin, JC; Mascola, JR; Shapiro, L; Kwong, PD

Published Date

  • April 16, 2013

Published In

Volume / Issue

  • 110 / 16

Start / End Page

  • 6470 - 6475

PubMed ID

  • 23536288

Pubmed Central ID

  • 23536288

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1219320110

Language

  • eng

Conference Location

  • United States