Omer Dushek
@tcell.bsky.social
Professor of Molecular Immunology at the University of Oxford.
Experiments & Math(s) to understand and exploit T cells.
Founder & Director of MatchBio Ltd
Experiments & Math(s) to understand and exploit T cells.
Founder & Director of MatchBio Ltd
Our new review article led by Jordan Kramer:
Platforms for studying cell–cell recognition by immune cells
onlinelibrary.wiley.com/doi/10.1111/...
Platforms for studying cell–cell recognition by immune cells
onlinelibrary.wiley.com/doi/10.1111/...
May 31, 2025 at 8:54 AM
Our new review article led by Jordan Kramer:
Platforms for studying cell–cell recognition by immune cells
onlinelibrary.wiley.com/doi/10.1111/...
Platforms for studying cell–cell recognition by immune cells
onlinelibrary.wiley.com/doi/10.1111/...
CombiCells allow combinatorial display of cell surface ligands
www.nature.com/articles/s41...
A new Tools of the Trade article from Nature Reviews Immunology by Sofía Bustamante Eguiguren in our lab highlights the CombiCell platform to combinatorially display and titrate many cell surface ligands
www.nature.com/articles/s41...
A new Tools of the Trade article from Nature Reviews Immunology by Sofía Bustamante Eguiguren in our lab highlights the CombiCell platform to combinatorially display and titrate many cell surface ligands
April 1, 2025 at 4:45 PM
CombiCells allow combinatorial display of cell surface ligands
www.nature.com/articles/s41...
A new Tools of the Trade article from Nature Reviews Immunology by Sofía Bustamante Eguiguren in our lab highlights the CombiCell platform to combinatorially display and titrate many cell surface ligands
www.nature.com/articles/s41...
A new Tools of the Trade article from Nature Reviews Immunology by Sofía Bustamante Eguiguren in our lab highlights the CombiCell platform to combinatorially display and titrate many cell surface ligands
Taken together, our 3D affinities enable us to resolve discrepancies between the OT-I and other TCRs used in the literature.
January 16, 2025 at 8:10 AM
Taken together, our 3D affinities enable us to resolve discrepancies between the OT-I and other TCRs used in the literature.
Our results underline the ability of T cells to effectively gauge proxies for 3D affinity within the 2D cell-cell interface, which is predicted by a model whereby the TCR/pMHC interactions are shielded by molecular forces (e.g. Pettmann et al (2023) EMBO J; Schrangl et al (2024) bioRxiv)
January 16, 2025 at 8:10 AM
Our results underline the ability of T cells to effectively gauge proxies for 3D affinity within the 2D cell-cell interface, which is predicted by a model whereby the TCR/pMHC interactions are shielded by molecular forces (e.g. Pettmann et al (2023) EMBO J; Schrangl et al (2024) bioRxiv)
We find high correlations between 3D affinities and 2D affinities, and with T cell responses. We don’t find a sharp affinity threshold but rather imperfect antigen discrimination. We show that the kinetic proofreading mechanism can explain this level of discrimination with high antigen sensitivity.
January 16, 2025 at 8:10 AM
We find high correlations between 3D affinities and 2D affinities, and with T cell responses. We don’t find a sharp affinity threshold but rather imperfect antigen discrimination. We show that the kinetic proofreading mechanism can explain this level of discrimination with high antigen sensitivity.
We find that the OT-I interaction with its foreign OVA antigen has physiological affinity (KD = 34 uM) with a short half-life (<1 s) and has a remarkably low affinity to positively selecting peptides (KD > 2000 uM).
January 16, 2025 at 8:10 AM
We find that the OT-I interaction with its foreign OVA antigen has physiological affinity (KD = 34 uM) with a short half-life (<1 s) and has a remarkably low affinity to positively selecting peptides (KD > 2000 uM).
In this study, we use a new method to accurately measure 3D TCR/pMHC affinities at 37C between OT-I and 19 peptides commonly used in the literature, including positively selecting self peptides.
January 16, 2025 at 8:10 AM
In this study, we use a new method to accurately measure 3D TCR/pMHC affinities at 37C between OT-I and 19 peptides commonly used in the literature, including positively selecting self peptides.
This raises critical questions about the generalizability of findings derived from the widely used OT-I system and its relevance to broader T cell biology.
January 16, 2025 at 8:10 AM
This raises critical questions about the generalizability of findings derived from the widely used OT-I system and its relevance to broader T cell biology.
Moreover, the OT-I interaction with its foreign OVA antigen was reported to have an extremely long half-life (~533 seconds at 37C) giving rise to the notion that it is an unusual TCR.
January 16, 2025 at 8:10 AM
Moreover, the OT-I interaction with its foreign OVA antigen was reported to have an extremely long half-life (~533 seconds at 37C) giving rise to the notion that it is an unusual TCR.
However, this degree of peripheral discrimination has not been observed in other, less commonly used TCRs, revealing a significant discrepancy between the OT-I TCR and other models (e.g. see Pettmann et al (2021) eLife, elifesciences.org/articles/67092).
January 16, 2025 at 8:10 AM
However, this degree of peripheral discrimination has not been observed in other, less commonly used TCRs, revealing a significant discrepancy between the OT-I TCR and other models (e.g. see Pettmann et al (2021) eLife, elifesciences.org/articles/67092).
Previous studies have suggested that OT-I T cells exhibit near-perfect discrimination between lower-affinity self and higher-affinity foreign antigens.
January 16, 2025 at 8:10 AM
Previous studies have suggested that OT-I T cells exhibit near-perfect discrimination between lower-affinity self and higher-affinity foreign antigens.
The OT-I TCR transgenic mouse model is one of the most widely used tools for studying all aspects of immunity, including central and peripheral tolerance, infection, cancer, vaccination, autoimmunity, and transplantation.
January 16, 2025 at 8:10 AM
The OT-I TCR transgenic mouse model is one of the most widely used tools for studying all aspects of immunity, including central and peripheral tolerance, infection, cancer, vaccination, autoimmunity, and transplantation.
Our new work!
The 3D affinities of the OT-I TCR to foreign and self-antigens predict their 2D affinities and reveal imperfect antigen discrimination
www.biorxiv.org/content/10.1...
The 3D affinities of the OT-I TCR to foreign and self-antigens predict their 2D affinities and reveal imperfect antigen discrimination
www.biorxiv.org/content/10.1...
January 16, 2025 at 8:10 AM
Our new work!
The 3D affinities of the OT-I TCR to foreign and self-antigens predict their 2D affinities and reveal imperfect antigen discrimination
www.biorxiv.org/content/10.1...
The 3D affinities of the OT-I TCR to foreign and self-antigens predict their 2D affinities and reveal imperfect antigen discrimination
www.biorxiv.org/content/10.1...
We also show that size-matching with CD2/CD58 is important for other receptor/ligand interactions, specifically PD-1/PD-L1: elongating PD-1 reduces its ability to inhibit the TCR but increases its ability to inhibit the CAR.
January 8, 2025 at 12:19 PM
We also show that size-matching with CD2/CD58 is important for other receptor/ligand interactions, specifically PD-1/PD-L1: elongating PD-1 reduces its ability to inhibit the TCR but increases its ability to inhibit the CAR.
Here, we show that the failure of CAR-T cells to exploit CD2/CD58 adhesion to increase sensitivity can be fixed by matching the physical size of CAR/antigen and CD2/CD58 complexes by elongating CD2 or compacting the CAR.
January 8, 2025 at 12:19 PM
Here, we show that the failure of CAR-T cells to exploit CD2/CD58 adhesion to increase sensitivity can be fixed by matching the physical size of CAR/antigen and CD2/CD58 complexes by elongating CD2 or compacting the CAR.
Our new work on optimising CAR-T cell sensitivity is now on bioRxiv!
Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes
biorxiv.org/cgi/content/...
Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes
biorxiv.org/cgi/content/...
January 8, 2025 at 12:19 PM
Our new work on optimising CAR-T cell sensitivity is now on bioRxiv!
Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes
biorxiv.org/cgi/content/...
Optimising CAR-T cell sensitivity by engineering matched extracellular sizes between CAR/antigen and CD2/CD58 adhesion complexes
biorxiv.org/cgi/content/...
Our work led by Anna Huhn is now published!
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
lnkd.in/epe8YZPm
Thank you to the reviewers for constructive feedback!
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
lnkd.in/epe8YZPm
Thank you to the reviewers for constructive feedback!
January 4, 2025 at 4:28 PM
Our work led by Anna Huhn is now published!
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
lnkd.in/epe8YZPm
Thank you to the reviewers for constructive feedback!
The molecular reach of antibodies crucially underpins their viral neutralisation capacity
lnkd.in/epe8YZPm
Thank you to the reviewers for constructive feedback!
Our new work!
We show that T cell cross-reactivity can be reduced without modifying the TCR itself (by dramatically enhancing antigen discrimination).
Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors
www.biorxiv.org/content/10.1...
We show that T cell cross-reactivity can be reduced without modifying the TCR itself (by dramatically enhancing antigen discrimination).
Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors
www.biorxiv.org/content/10.1...
November 20, 2024 at 9:55 AM
Our new work!
We show that T cell cross-reactivity can be reduced without modifying the TCR itself (by dramatically enhancing antigen discrimination).
Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors
www.biorxiv.org/content/10.1...
We show that T cell cross-reactivity can be reduced without modifying the TCR itself (by dramatically enhancing antigen discrimination).
Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors
www.biorxiv.org/content/10.1...
Our new work!
Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells
biorxiv.org/content/10.1...
X Thread: x.com/Dushek/statu...
Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells
biorxiv.org/content/10.1...
X Thread: x.com/Dushek/statu...
February 26, 2024 at 11:32 AM
Our new work!
Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells
biorxiv.org/content/10.1...
X Thread: x.com/Dushek/statu...
Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells
biorxiv.org/content/10.1...
X Thread: x.com/Dushek/statu...
Our new work is now published in EMBO Journal!
We describe a method for combinatorial display and titration of ligands directly on the surface of cells.
We use it to study T-cell antigen sensitivity and the contribution of co-stimulation/inhibition receptors.
www.embopress.org/doi/full/10....
We describe a method for combinatorial display and titration of ligands directly on the surface of cells.
We use it to study T-cell antigen sensitivity and the contribution of co-stimulation/inhibition receptors.
www.embopress.org/doi/full/10....
December 21, 2023 at 8:36 AM
Our new work is now published in EMBO Journal!
We describe a method for combinatorial display and titration of ligands directly on the surface of cells.
We use it to study T-cell antigen sensitivity and the contribution of co-stimulation/inhibition receptors.
www.embopress.org/doi/full/10....
We describe a method for combinatorial display and titration of ligands directly on the surface of cells.
We use it to study T-cell antigen sensitivity and the contribution of co-stimulation/inhibition receptors.
www.embopress.org/doi/full/10....