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Immunoglobulin Gene Insertions and Deletions in the Affinity Maturation of HIV-1 Broadly Reactive Neutralizing Antibodies.
- Source :
- Cell Host & Microbe; Sep2014, Vol. 16 Issue 3, p304-313, 10p
- Publication Year :
- 2014
-
Abstract
- Summary Induction of HIV-1 broad neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development but has remained challenging partially due to unusual traits of bnAbs, including high somatic hypermutation (SHM) frequencies and in-frame insertions and deletions (indels). Here we examined the propensity and functional requirement for indels within HIV-1 bnAbs. High-throughput sequencing of the immunoglobulin (Ig) V H DJ H genes in HIV-1 infected and uninfected individuals revealed that the indel frequency was elevated among HIV-1-infected subjects, with no unique properties attributable to bnAb-producing individuals. This increased indel occurrence depended only on the frequency of SHM point mutations. Indel-encoded regions were generally proximal to antigen binding sites. Additionally, reconstruction of a HIV-1 CD4-binding site bnAb clonal lineage revealed that a large compound V H DJ H indel was required for bnAb activity. Thus, vaccine development should focus on designing regimens targeted at sustained activation of bnAb lineages to achieve the required SHM and indel events. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19313128
- Volume :
- 16
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Cell Host & Microbe
- Publication Type :
- Academic Journal
- Accession number :
- 98140521
- Full Text :
- https://doi.org/10.1016/j.chom.2014.08.006