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Printable Handouts
Navigable Slide Index
- Introduction
- FcRs bind the Fc domain of antibodies
- Types of mouse FcRs
- Cell expression of mouse FcRs
- Types of human FcRs
- Cell expression of human FcRs
- FcγRs: a family of related receptors that bind IgG
- FcγRs: affinity for IgG
- FcγRs: paralogous system in mice
- FcγRs: IgG binding is regulated by carbohydrate
- FcγR regulate many facets of the immune response
- FcγRII regulates many facets of the immune response
- ITAM vs ITIM Signaling through FcγR
- Consequences of FcγR ligation on NK cells
- Consequences of FcγR ligation on B cells
- Consequences of FcγR ligation on additional immune cells
- Cellular modulation of FcγR respons
- Genetic modulation of FcγR response
- Human FcγR are polymorphic and have copy number variation
- Isotype modulation of FcγR response
- mAb isotype dictates FcγR binding
- hAb isotype dictates FcγR binding
- The antibody revolution
- Currently approved mAbs for cancer
- How do direct targeting mAb work?
- Importance of FcγR (1)
- Importance of FcγR (2)
- Evidence for the importance of FcγR in mAb therapy (1)
- Evidence for the importance of FcγR in mAb therapy (2)
- Evidence for the importance of FcγR in mAb therapy (3)
- Direct targeting mAb
- Improving FcγR effector functions
- Improving effector functions using fucosylation
- Impact of glyco-engineering on OBZ
- Structural basis for enhanced affinity of glycoengineered antibodies for FcγRIIIa
- OBZ exhibits up to 100-fold higher ADCC potency than rituximab and ofatumumab
- Summary of mAb therapeutics
- Interaction of immunomodulatory mAb with FcγR
- Immunomodulatory mAb
- Two classes of Immunomodulatory mAbs
- Both classes of immunomodulatory mAbs can be therapeutic
- Optimal isotypes of checkpoint mAbs differ
- Contrasting isotype requirements for immune stimulatory mAb
- The role of FcγRIIb is in crosslinking
- Mechanism of agonistic anti-TNFR mAb
- Summary
- Thank you
Topics Covered
- Cellular expression and function of Fc gamma receptors (FcγRs)
- IgG binding to FcγRs is modulated by carbohydrates
- The consequences of FcγR ligation in immune cells is cell type specific
- Roles of FcγRs in sculpting in the humoral immune response
- FcγRs is a key regulator in antibody immunotherapy
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Cragg, M. (2021, January 31). The immunobiology of Fc receptors [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/XVMF9971.Export Citation (RIS)
Publication History
Financial Disclosures
- Mark Cragg is a retained consultant for BioInvent International and has performed educational and advisory roles for Baxalta and Boehringer Ingleheim. He has received research funding from Roche, Gilead, Bioinvent International and GSK.
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
Please wait while the transcript is being prepared...
0:00
I'm Professor Mark Cragg.
I'm a professor of experimental cancer biology at the Antibody and Vaccine
Group in the Centre of Cancer Immunology in the University of Southampton.
The talk that I'm going to give today is around the immunobiology of Fc receptors.
0:16
Fc receptors bind the Fc domain of antibodies.
I'm sure you're all aware of the structure of an antibody.
It's this Y-shaped molecule which has Fab domains
which do the binding of the antibody,
which bind to different epitopes and antigens,
which carry the variable regions,
whereas we also have the stem part of
the antibody molecule, known as the Fc or fragment crystallizable.
It's that fragment crystallizable,
the Fc domain, which is bound by Fc receptors.
Importantly, Fc receptors are able to bind to different classes of antibody.
You can see that there are a number of different classes of antibody, IgA, D,
E, G, and M, and each of them have different functions within the immune system.
For example, IgA protects mucous membranes,
whereas IgM is a key component of the primary immune response,
and IgG of the secondary antibody response.
But it's important to recognise that several of
their key functions are actually mediated by Fc receptors.
1:20
In the mouse system,
there are a whole host of
Fc receptors that can bind to those different antibody molecules.
There are a whole series which are isotype-specific.
For example, a polyIgR is
an Fc receptor which can bind to IgM molecules and also IgA molecules.
In contrast, we have receptors such as Fc epsilon receptor I (FcεRI) and Fc epsilon receptor II (FcεRII),
which bind only to IgE molecules.
We also have a whole series of receptors which bind to the Fc gamma receptors,
which bind to IgG,
and I'm going to be spending a lot of time talking about those in the later slides.
It's also important to say that there's an intracellular Fc receptor called TRIM21,
which binds antibodies when they've been internalised
(after they have bound to viruses
for instance), and that stimulates an antiviral response.
But we're not going to get into that particular Fc receptor in any great detail.