Download MendeleyMultidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies.
Zhou, T., Zhu, J., Wu, X., Moquin, S., Zhang, B., Acharya, P., Georgiev, I.S., Altae-Tran, H.R., Chuang, G.Y., Joyce, M.G., Do Kwon, Y., Longo, N.S., Louder, M.K., Luongo, T., McKee, K., Schramm, C.A., Skinner, J., Yang, Y., Yang, Z., Zhang, Z., Zheng, A., Bonsignori, M., Haynes, B.F., Scheid, J.F., Nussenzweig, M.C., Simek, M., Burton, D.R., Koff, W.C., Mullikin, J.C., Connors, M., Shapiro, L., Nabel, G.J., Mascola, J.R., Kwong, P.D.(2013) Immunity 39: 245-258
- PubMed: 23911655
- DOI: https://doi.org/10.1016/j.immuni.2013.04.012
- Primary Citation of Related Structures:
4LSP, 4LSQ, 4LSR, 4LSS, 4LST, 4LSU, 4LSV - PubMed Abstract:
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.
Organizational Affiliation:
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
