期刊
MOLECULAR IMMUNOLOGY
卷 70, 期 -, 页码 94-103出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2015.12.002
关键词
HIV; Antibodies; Human; Neutralization; Monoclonal antibodies; B cells
资金
- NCATS NIH HHS [UL1 TR001414] Funding Source: Medline
- NIAID NIH HHS [P30-AI50409, NIH K08 AI083078, P30 AI050409, R01 AI-102715, P30 AI-054999, K08 AI083078, P30 AI054999, U01 AI-078407, R01 AI102715, U01 AI078407, P30 AI110527] Funding Source: Medline
Neutralizing antibodies (Abs) are thought to be a critical component of an appropriate HIV vaccine response. It has been proposed that Abs recognizing conformationally dependent quaternary epitopes on the HIV envelope (Env) trimer may be necessary to neutralize diverse HIV strains. A number of recently described broadly neutralizing monoclonal Abs (mAbs) recognize complex and quaternary epitopes. Generally, many such Abs exhibit extensive numbers of somatic mutations and unique structural characteristics. We sought to characterize the native antibody (Ab) response against circulating HIV focusing on such conformational responses, without a prior selection based on neutralization. Using a capture system based on VLPs incorporating cleaved envelope protein, we identified a selection of B cells that produce quaternary epitope targeting Abs (QtAbs). Similar to a number of broadly neutralizing Abs, the Ab genes encoding these QtAbs showed extensive numbers of somatic mutations. However, when expressed as recombinant molecules, these Abs failed to neutralize virus or mediate ADCVI activity. Molecular analysis showed unusually high numbers of mutations in the Ab heavy chain framework 3 region of the variable genes. The analysis suggests that large numbers of somatic mutations occur in Ab genes encoding HIV Abs in chronically infected individuals in a non-directed, stochastic, manner. (C) 2015 Elsevier Ltd. All rights reserved.
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