Details

Autor(en) / Beteiligte

• Zhou, Tongqing
• Zhu, Jiang
• Wu, Xueling
• Moquin, Stephanie
• Zhang, Baoshan
• Acharya, Priyamvada
• Georgiev, Ivelin S.
• Altae-Tran, Han R.
• Chuang, Gwo-Yu
• Joyce, M. Gordon
• Kwon, Young Do
• Longo, Nancy S.
• Louder, Mark K.
• Luongo, Timothy
• McKee, Krisha
• Schramm, Chaim A.
• Skinner, Jeff
• Yang, Yongping
• Yang, Zhongjia
• Zhang, Zhenhai
• Zheng, Anqi
• Bonsignori, Mattia
• Haynes, Barton F.
• Scheid, Johannes F.
• Nussenzweig, Michel C.
• Simek, Melissa
• Burton, Dennis R.
• Koff, Wayne C.
• Mullikin, James C.
• Connors, Mark
• Shapiro, Lawrence
• Nabel, Gary J.
• Mascola, John R.
• Kwong, Peter D.

Titel

Multi-donor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for Effective HIV-1 Neutralization by VRCO1-class Antibodies

Ist Teil von

• Immunity (Cambridge, Mass.), 2013-08, Vol.39 (2), p.245-258

Erscheinungsjahr

2013

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10 12 antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few—likely one—ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population.