Journal
IMMUNITY
Volume 39, Issue 2, Pages 245-258Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2013.04.012
Keywords
-
Categories
Funding
- Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases
- National Human Genome Research Institute, National Institutes of Health
- International AIDS Vaccine Initiative's Neutralizing Antibody Consortium
- Center for HIV/AIDS Vaccine Immunology Grant from the National Institutes from Health [AI 5U19 AI 067854-06]
- US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available