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A new panel of epitope mapped monoclonal antibodies recognising the prototypical tetraspanin CD81
- Source :
- Wellcome Open Research, Europe PubMed Central
- Publication Year :
- 2017
-
Abstract
- Background:Tetraspanins are small transmembrane proteins, found in all higher eukaryotes, that compartmentalize cellular membranes through interactions with partner proteins. CD81 is a prototypical tetraspanin and contributes to numerous physiological and pathological processes, including acting as a critical entry receptor for hepatitis C virus (HCV). Antibody engagement of tetraspanins can induce a variety of effects, including actin cytoskeletal rearrangements, activation of MAPK-ERK signaling and cell migration. However, the epitope specificity of most anti-tetraspanin antibodies is not known, limiting mechanistic interpretation of these studies.Methods:We generated a panel of monoclonal antibodies (mAbs) specific for CD81 second extracellular domain (EC2) and performed detailed epitope mapping with a panel of CD81 mutants. All mAbs were screened for their ability to inhibit HCV infection and E2-CD81 association. Nanoscale distribution of cell surface CD81 was investigated by scanning electron microscopy.Results:The antibodies were classified in two epitope groups targeting opposing sides of EC2. We observed a wide range of anti-HCV potencies that were independent of their epitope grouping, but associated with their relative affinity for cell-surface expressed CD81. Scanning electron microscopy identified at least two populations of CD81; monodisperse and higher-order assemblies, consistent with tetraspanin-enriched microdomains.Conclusions:These novel antibodies provide well-characterised tools to investigate CD81 function, including HCV entry, and have the potential to provide insights into tetraspanin biology in general.
- Subjects :
- 0301 basic medicine
hepatitis C virus
medicine.drug_class
viruses
Medicine (miscellaneous)
Monoclonal antibody
General Biochemistry, Genetics and Molecular Biology
Epitope
03 medical and health sciences
CD81
Tetraspanin
Medicine
Antigen Processing & Recognition
Cytoskeleton
030102 biochemistry & molecular biology
biology
Viral Infections (without HIV)
business.industry
Articles
Transmembrane protein
3. Good health
Cell biology
030104 developmental biology
Epitope mapping
tetraspanin
biology.protein
Antibody
business
Research Article
Subjects
Details
- ISSN :
- 2398502X
- Database :
- OpenAIRE
- Journal :
- Wellcome Open Research
- Accession number :
- edsair.doi.dedup.....712010180d6fa3650f63b5b892e55f86
- Full Text :
- https://doi.org/10.12688/wellcomeopenres.12058.1