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 Concept Videos

Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Transcytosis of IgG01:15

Transcytosis of IgG

Transcytosis is the process in which molecules are internalized by endocytosis, transported across the cell, and released through exocytosis from the opposite end of the cell. Molecules such as insulin, immunoglobulins, and certain nutrients are transferred through the recycling endosomes by recycling and transcytosis.
IgG molecules from a mother undergo transcytosis starting around 13 weeks of gestation. The amount of IgG transferred and entering the fetal blood circulation increases with...
Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...

You might also read

Related Articles

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

Sort by
Same author

An integrated, scaled approach to resolve TSC2 variants of uncertain significance.

Nature communications·2026
Same author

Saturation Genome Editing reveals the functional impact of RAD51D <i>and</i> XRCC2 variants.

bioRxiv : the preprint server for biology·2026
Same author

First-line durvalumab in combination with trastuzumab deruxtecan in women with locally advanced unresectable or metastatic, hormone-receptor-negative, HER2-low breast cancer: multicenter, open-label, phase 1b/2 BEGONIA platform trial.

Nature cancer·2026
Same author

Durvalumab Plus Paclitaxel, with or without Capivasertib or Oleclumab, in Patients with Locally Advanced/Metastatic Triple-Negative Breast Cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research·2026
Same author

Pan-cancer analysis in the real-world setting uncovers immunogenomic drivers of acquired resistance post-immunotherapy.

Journal for immunotherapy of cancer·2026
Same author

Gene- and domain-aware calibration increases the clinical utility of variant effect predictors.

Research square·2026

Related Experiment Video

Updated: Jun 1, 2026

Assessment of Human Natural Killer Cell Events Driven by Fc&#947;RIIIa Engagement in the Presence of Therapeutic Antibodies
09:54

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies

Published on: May 22, 2020

A variant human IgG1-Fc mediates improved ADCC.

Ross Stewart1, George Thom, Michaela Levens

  • 1MedImmune, Granta Park, Cambridge, UK. stewartr@medimmune.com

Protein Engineering, Design & Selection : PEDS
|May 21, 2011
PubMed
Summary

Engineered antibodies show enhanced binding to FcγRIIIa, boosting antibody-dependent cellular cytotoxicity (ADCC). A specific variant, 125_B01, improves ADCC activity across FcγRIIIa allotypes.

More Related Videos

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
04:47

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies

Published on: February 23, 2018

Assessing Antibody-dependent, Cell-mediated Cytotoxicity in Cancer Cells using Antibody-Dependent Cell-Mediated Cytotoxicity Reporter Bioassay
05:21

Assessing Antibody-dependent, Cell-mediated Cytotoxicity in Cancer Cells using Antibody-Dependent Cell-Mediated Cytotoxicity Reporter Bioassay

Published on: September 13, 2024

Related Experiment Videos

Last Updated: Jun 1, 2026

Assessment of Human Natural Killer Cell Events Driven by Fc&#947;RIIIa Engagement in the Presence of Therapeutic Antibodies
09:54

Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies

Published on: May 22, 2020

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
04:47

A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies

Published on: February 23, 2018

Assessing Antibody-dependent, Cell-mediated Cytotoxicity in Cancer Cells using Antibody-Dependent Cell-Mediated Cytotoxicity Reporter Bioassay
05:21

Assessing Antibody-dependent, Cell-mediated Cytotoxicity in Cancer Cells using Antibody-Dependent Cell-Mediated Cytotoxicity Reporter Bioassay

Published on: September 13, 2024

Area of Science:

  • Immunology
  • Protein Engineering
  • Biochemistry

Background:

  • The Fc region of immunoglobulin G (IgG1) interacts with FcγRIIIa on natural killer cells to mediate antibody-dependent cellular cytotoxicity (ADCC).
  • Improving FcγRIIIa binding enhances ADCC, a crucial mechanism for therapeutic antibodies.

Purpose of the Study:

  • To engineer improved human IgG1 Fc variants with enhanced binding to human FcγRIIIa using ribosome display.
  • To characterize the functional impact of these variants on ADCC activity.

Main Methods:

  • Ribosome display was employed to select IgG1 Fc variants with improved binding to FcγRIIIa from a library generated by error-prone PCR.
  • Binding affinities were assessed using radioimmunoassay and AlphaScreen assays.
  • Functional ADCC activity of engineered antibodies was evaluated in cell-based assays.

Main Results:

  • Several IgG1 Fc variants demonstrated improved binding to FcγRIIIa compared to wild-type.
  • A specific variant, 125_B01, exhibited significantly enhanced ADCC activity, with a four-fold reduced EC50 and increased maximal lysis.
  • The enhanced function of 125_B01 was attributed to a Phe243Leu substitution in the CH2 domain, which also influenced glycosylation patterns.

Conclusions:

  • Engineered IgG1 Fc variants can significantly enhance FcγRIIIa binding and ADCC activity.
  • The Phe243Leu substitution is a key driver of improved FcγRIIIa binding and ADCC, potentially through altered glycosylation.
  • These findings offer a strategy for developing more potent therapeutic antibodies targeting FcγRIIIa-expressing cells.