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Sequencing HIV-neutralizing antibody exons and introns reveals detailed aspects of lineage maturation.

Nat Commun. 2018; 
Johnson EL, Doria-Rose NA, Gorman J, Bhiman JN,, Schramm CA, Vu AQ,, Law WH,, Zhang B, Bekker V, Abdool Karim SS,, Ippolito GC, Morris L,,, Moore PL,,, Kwong PD, Mascola JR, Georgiou G,,.
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摘要

The developmental pathways of broadly neutralizing antibodies (bNAbs) against HIV are of great importance for the design of immunogens that can elicit protective responses. Here we show the maturation features of the HIV-neutralizing anti-V1V2 VRC26 lineage by simultaneously sequencing the exon together with the downstream intron of VRC26 members. Using the mutational landscapes of both segments and the selection-free nature of the intron region, we identify multiple events of amino acid mutational convergence in the complementarity-determining region 3 (CDR3) of VRC26 members, and determine potential intermediates with diverse CDR3s to a late stage bNAb from 2 years prior to its isolation. Moreover, we functio... More

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