Nonspecificity in a nonimmune human scFv repertoire.
MAbs
; 9(7): 1029-1035, 2017 10.
Article
em En
| MEDLINE
| ID: mdl-28910564
ABSTRACT
Efforts to develop effective antibody therapeutics are frequently hampered by issues such as aggregation and nonspecificity, often only detected in late stages of the development process. In this study, we used a high throughput cross-reactivity assay to select nonspecific clones from a naïve human repertoire scFv library displayed on the surface of yeast. Most antibody families were de-enriched; however, the rarely expressed VH6 family was highly enriched among nonspecific clones, representing almost 90% of isolated clones. Mutational analysis of this family reveals a dominant role of CDRH2 in driving nonspecific binding. Homology modeling of a panel of VH6 antibodies shows a constrained ß-sheet structure in CDRH2 that is not present in other families, potentially contributing to nonspecificity of the family. These findings confirm the common decision to exclude VH6 from synthetic antibody libraries, and support VH6 polyreactivity as a possible important role for the family in early ontogeny and cause for its overabundance in cases of some forms of autoimmunity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos de Cadeia Única
/
Especificidade de Anticorpos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article