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Volumn 340, Issue 6133, 2013, Pages 751-756

Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization

(25)  Georgiev, Ivelin S a   Doria Rose, Nicole A a   Zhou, Tongqing a   Kwon, Young Do a   Staupe, Ryan P a   Moquin, Stephanie a   Chuang, Gwo Yu a   Louder, Mark K a   Schmidt, Stephen D a   Altae Tran, Han R a   Bailer, Robert T a   McKee, Krisha a   Nason, Martha a   O'Dell, Sijy a   Ofek, Gilad a   Pancera, Marie a   Srivatsan, Sanjay a   Shapiro, Lawrence a,b   Connors, Mark a   Migueles, Stephen A a   more..


Author keywords

[No Author keywords available]

Indexed keywords

NEUTRALIZING ANTIBODY;

EID: 84877618448     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1233989     Document Type: Article
Times cited : (190)

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    • One of the features of our approach is its ability to distinguish between antibodies targeting overlapping epitopes in a substantially different ways: There is a significant difference in the correlation coefficients for antibodies targeting a similar epitope versus the correlation coefficients for antibodies targeting different epitopes on the same site of vulnerability. Similarly, there is a significant difference for similar epitopes versus different sites of vulnerability; however, there is no significant difference for different epitopes on the same site of vulnerability versus different sites of vulnerability (fig. S1).
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    • To resolve the discrepancy between epitope mapping and neutralization-based predictions, we determined the cocrystal structure of VRC06 in complex with the gp120 core and compared it with the structure of the VRC01-like antibody VRC03: The antibody variable-domain root mean square deviation upon alignment of the respective VRC06- and VRC03-bound gp120 cores was 1.45 Å, confirming the similarity in the modes of gp120 recognition by these two antibodies (Fig. 2B and table S3). Although VRC03 and VRC06 exhibit extraordinary similarity in their mode of recognition of gp120 when compared with VRC01, unlike VRC01, antibodies VRC03 and VRC06 contain a long insertion in the heavy-chain framework 3 region that falls in the vicinity of the gp120 bridging sheet. In the crystallized complexes of these antibodies and monomeric gp120 core (which lacks the full V1/V2 region), the insertions do not make substantial contact with gp120. On the functional trimer spike, however, these insertions likely make additional contacts with the antigen, extending the antibody epitopes as compared with VRC01. The result is that VRC03 and VRC06 cluster in the periphery of the VRC01 cluster.
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    • A signal for PGT128-like antibodies in donor 45 was also observed. However, only part of the neutralization activity of the donor 45 serum could be attributed to VRC01-like antibodies (fig. S11), which indicated that other antibody specificities may also exist in that serum. It is thus not surprising to observe other neutralization signals in the predictions.
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    • The current analysis is validated primarily for a single major component-antibody specificity in serum, with predictions on other specificities yet to be ascertained; however, the ability to extract major specificities from polyclonal sera will likely be of considerable utility. Nevertheless, the observation that antibody neutralization fingerprints can capture sufficient information to allow, at least in some cases, the deconvolution of the polyclonal serum-based pattern of HIV-1 neutralization into neutralization from component antibodies is subject to a number of assumptions and limitations (41).
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* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.