Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Engineering therapeutic antibodies for improved function.

L G Presta1, R L Shields, A K Namenuk

  • 1Genentech, Inc., South San Francisco, CA 94080, USA. leonard.presta@dnax.org

Biochemical Society Transactions
|August 28, 2002
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

[Clinical challenges and research progress in variants of uncertain significance of inherited cardiovascular diseases].

Zhonghua xin xue guan bing za zhi·2026
Same author

[Essentials and considerations for outpatient genetic counseling for inherited cardiovascular diseases].

Zhonghua xin xue guan bing za zhi·2026
Same author

[Distribution characteristics of PKP2 non-synonymous variations in protein domain and genotype-phenotype relationship in patients with arrhythmogenic right ventricular cardiomyopathy].

Zhonghua xin xue guan bing za zhi·2026
Same author

Intermediate-term risk of cardiac allograft vasculopathy following heart transplantation from hepatitis C viremic donors in the era of direct-acting antiviral therapy.

JHLT open·2025
Same author

[Sperm donation utilization rates in nonobstructive azoospermia patients under different testicular sperm retrieval methods during assisted reproductive technology cycles].

Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences·2025
Same author

[Electrocardiographic characteristics of cardiomyopathy].

Zhonghua xin xue guan bing za zhi·2025
Same journal

TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.

Biochemical Society transactions·2026
Same journal

Advancing the monitoring of organelle contact sites in vitro and in vivo.

Biochemical Society transactions·2026
Same journal

Mechanisms influencing transient cytoplasmic protein targeting to intracellular lipid droplets.

Biochemical Society transactions·2026
Same journal

Replication associated nuclear DNA mismatch repair across kingdoms.

Biochemical Society transactions·2026
Same journal

Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.

Biochemical Society transactions·2026
Same journal

Implications of Rho GTPase signaling in cancer immunotherapy.

Biochemical Society transactions·2026
See all related articles

Researchers mapped human IgG1 binding sites for Fc gamma receptors (Fc gamma R), identifying common and distinct residues. Engineered IgG1 variants enhanced Fc gamma RIIIa binding and improved antibody-dependent cellular cytotoxicity (ADCC) in vitro.

Area of Science:

  • Immunology
  • Structural Biology
  • Protein Engineering

Background:

  • Antibody Fc domains mediate effector functions through interactions with Fc receptors.
  • Understanding these interactions is crucial for developing targeted immunotherapies.

Purpose of the Study:

  • To map the binding sites of human IgG1 on various Fc gamma receptors (Fc gamma RI, Fc gamma RIIa, Fc gamma RIIb, Fc gamma RIIIa) and the neonatal Fc receptor.
  • To engineer IgG1 variants with modified Fc gamma receptor binding properties.
  • To assess the impact of engineered binding on antibody-dependent cellular cytotoxicity (ADCC).

Main Methods:

  • Site-directed mutagenesis of human IgG1.
  • Binding assays to Fc gamma receptors and neonatal FcR.
  • In vitro antibody-dependent cellular cytotoxicity (ADCC) assays using peripheral blood mononuclear cells and natural killer cells.

Related Experiment Videos

Main Results:

  • A common set of IgG1 residues mediates binding to all Fc gamma receptors, with distinct sites utilized by Fc gamma RII and Fc gamma RIII.
  • Specific IgG1 mutations were identified that either abrogated, improved, or differentially modulated binding to Fc gamma receptors.
  • Engineered IgG1 variants with enhanced Fc gamma RIIIa binding demonstrated improved ADCC activity.

Conclusions:

  • The study delineates specific IgG1 residues critical for Fc gamma receptor interactions.
  • Engineering IgG1 binding sites can modulate Fc gamma receptor affinity and enhance ADCC.
  • These findings provide a basis for designing next-generation antibody therapeutics with improved effector functions.