Omer Dushek

If you're a postdoc interested in starting your own group, please consider the Dunn School at Oxford, UK.

It's a fantastic department and university for molecular immunology and all aspects of immune research!

Temporal control of cytokine production is lost in 2nd-gen CAR-T cells, says Patel et al. This could be key to understanding their efficacy and toxicity in cancer immunotherapy. 🧬

🔗 https://bit.ly/4lOLicw

#CancerImmunotherapy

Thanks to our funding, collaborators, constructive reviewers, and for the very efficient process at Immunology & Cell Biology!

By comparing the advantages and limitations of each platform, we provide a framework to choose the most suitable system to study signal integration in both basic and translational contexts.

A recently developed CombiCell system enables easy manipulation of ligands while conserving key biophysical properties.

In contrast, solid surfaces or supported lipid bilayers allow easy manipulation of ligands but lack the biophysical properties of cells, such as softness, a glycocalyx, and/or ligand mobility.

Although genetically modified antigen-presenting cells (APCs) offer the most physiological system, manipulating their ligands is difficult and slow.

We review and compare the available platforms, focusing on T-cell recognition.

Since they encounter a huge variety of normal and abnormal cells, they experience many different combinations and concentrations of ligands.

Understanding immune responses therefore requires platforms that enable ligands to be easily manipulated.

Immune cells interact directly with other cells and make decisions by integrating information from many different receptor–ligand interactions at these cell–cell interfaces.

Our new review article led by Jordan Kramer:

Platforms for studying cell–cell recognition by immune cells

onlinelibrary.wiley.com/doi/10.1111/...

biomembrane-days-2025.mpikg.mpg.de

📢 Registration is open for the Biomembrane Days 2025!
🔗 biomembrane-days-2025.mpikg.mpg.de

A top-notch lineup of speakers, 120 posters, 200 scientists.
📜Submit an abstract by July 14
🏆3 Poster prizes
⚠️Limited spots-previous events were fully booked!

#BiomembraneDays2025 #Biophysics #CellMembranes

Using CombiCells, a platform for titration and combinatorial display of cell surface ligands, to study T-cell antigen sensitivity modulation by accessory receptors | The EMBO Journal imageimageThe inherent difficulty in manipulating cell surface proteins limits our ability to study cell–cell recognition. This work develops a platform for the combinatorial display of cell surface l...

The original manuscript was published in @embojournal.org EMBO Journal last year

Using CombiCells, a platform for titration and combinatorial display of cell surface ligands, to study T-cell antigen sensitivity modulation by accessory receptors

www.embopress.org/doi/full/10....

Sofia has been exploiting the platform to study T cell signal integration by co-signalling receptor/ligand interactions.

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

The molecular reach of antibodies crucially underpins their viral neutralisation capacity

Our work on measuring and understanding the role of molecular reach on antibody function is now part of a list of editor's pick manuscripts:
www.nature.com/collections/...

A fantastic EACR conference that focuses on all aspects of immune responses to cancer!

Barcelona - May 2025

In vivo engineering of murine T cells using the evolved adeno-associated virus variant Ark313 Genetic engineering of T cells in mouse models is essential for investigating immune mechanisms. We aimed to develop an approach to manipulate T cells…

🚨New paper alert! 🚨 Our latest work in
@cp-immunity.bsky.social shows that Ark313, an evolved AAV variant enables in vivo genetic engineering of murine T cells! 🧵👇

sciencedirect.com/science/arti...

📢 LAST CHANCE to submit your abstracts for BSI Oxford and
@immunologyoxford.bsky.social's #OIS25 Symposium

This is your opportunity to take part in this celebration Oxford's outstanding #immunology research 🔬

Submissions are open until midnight on Friday 7th Feb 👉 bit.ly/4elJmnG

📢 Abstract submission for BSI Oxford and @immunologyoxford.bsky.social 's #OIS25 Symposium closes NEXT WEEK (7 Feb)

Don't miss your chance to take part in this celebration of the outstanding #immunology research happening across Oxford 💫

Submit your abstract here 👉 bit.ly/4elJmnG

How to Apply and Funding

Two weeks to go until the application deadline for ILESLA. If you or anyone you know would benefit from full funding to carry out a PhD in Life and/or Environmental Science please visit/refer to our website page iles.web.ox.ac.uk/how-apply where you can see open day videos and get full guidance.

We just can't stop recruiting!

Associate professor in cell and molecular biology @dunnschool, with a preference for immunology, inflammation and/or infection - all defined broadly

Come and be our colleague

Deadline 28 Feb, please spread the word

www.path.ox.ac.uk/vacancy/asso...

The OT-I TCR is often criticised as being very high-affinity and displaying unusual behaviour compared to other TCR transgenics. New work from @tcell.bsky.social shows this might not be the case. Will I still use OT-I and all the wonderful tools associated with it? Yes I will!

This was a fantastic effort led by Anna Huhn and a collaboration with @gerardlab.bsky.social. We thanks for our funders @wellcometrust.bsky.social Wellcome Trust and our fantastic department @dunnschool.bsky.social Dunn School

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)

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).

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.