Enzymatization of mouse monoclonal antibodies to the corresponding catalytic antibodies.
Animals
Mice
Antibodies, Monoclonal
/ immunology
Antibodies, Catalytic
/ metabolism
Hemagglutinin Glycoproteins, Influenza Virus
/ immunology
Mutagenesis, Site-Directed
Influenza A virus
/ immunology
Catalytic Domain
Humans
Immunoglobulin Light Chains
/ genetics
Antibodies, Viral
/ immunology
Mice, Inbred BALB C
Catalytic antibody
Förster resonance energy transfer substrate
Hemagglutinin
Influenza virus
Monoclonal antibody
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 May 2024
28 May 2024
Historique:
received:
21
03
2024
accepted:
24
05
2024
medline:
29
5
2024
pubmed:
29
5
2024
entrez:
28
5
2024
Statut:
epublish
Résumé
Catalytic antibodies possess a dual function that enables both antigen recognition and degradation. However, their time-consuming preparation is a significant drawback. This study developed a new method for quickly converting mice monoclonal antibodies into catalytic antibodies using site-directed mutagenesis. Three mice type monoclonal antibodies targeting hemagglutinin molecule of influenza A virus could be transformed into the catalytic antibodies by deleting Pro95 in CDR-3 of the light chain. No catalytic activity was observed for monoclonal antibodies and light chains. In contrast, the Pro95-deleted light chains exhibited a catalytic activity to cleave the antigenic peptide including the portion of conserved region of hemagglutinin molecule. The affinity of the Pro95-deleted light chains to the antigen increased approximately 100-fold compared to the wild-type light chains. In the mutants, three residues (Asp1, Ser92, and His93) come closer to the appropriate position to create the catalytic site and contributing to the enhancement of both catalytic function and immunoreactivity. Notably, the Pro95-deleted catalytic light chains could suppress influenza virus infection in vitro assay, whereas the parent antibody and the light chain did not. This strategy offers a rapid and efficient way to create catalytic antibodies from existing antibodies, accelerating the development for various applications in diagnostic and therapeutic applications.
Identifiants
pubmed: 38806597
doi: 10.1038/s41598-024-63116-6
pii: 10.1038/s41598-024-63116-6
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Catalytic
0
Hemagglutinin Glycoproteins, Influenza Virus
0
Immunoglobulin Light Chains
0
Antibodies, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12184Subventions
Organisme : Japan Science and Technology Agency
ID : JST-CREST Programs (Precise arrangement toward functionality)
Informations de copyright
© 2024. The Author(s).
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