Learning the Principles of T Cell Antigen Discernment T cells are central to the adaptive immune response, capable of detecting pathogenic antigens while ignoring healthy tissues with remarkable specificity and sensitivity. Quantitatively understanding h...

Happy to share our latest review article, “Learning the Principles of T Cell Antigen Discernment.” www.annualreviews.org/content/jour...
with @fxpbourassa.bsky.social , Sooraj Achar and Grégoire Altan-Bonnet ! 1/4

We hope our focus on fluctuating odors will inspire more experiments with naturalistic temporal statistics in olfactory mixtures. On the theory side, the manifold learning concept may inform background filtering strategies in other biological and artificial systems.

We then dissect, numerically and analytically, the dynamics and stability of these models (detailed Appendix!). Notably, we find that local interneurons endowed with the IBCM learning rule decompose the background by selecting individual odors.

We combine biologically plausible models of synaptic plasticity to implement this strategy in the early olfactory circuit. Simulating these learning rules show they greatly improve the recognition of new odors in fluctuating backgrounds.

Our proposal: manifold learning is optimal against fast fluctuations in high-dimensional olfactory space. Instead of filtering by anticipating inputs, a better strategy is to learn the low-dimensional manifold of background odors and suppress input projections in that subspace.

Due to turbulent transport, natural odor signals are intermittent and vary rapidly. Yet, animals filter out backgrounds with such fluctuations to discern new, relevant olfactory cues. How does that work?

Schematic of the early olfactory circuit with local interneurons inhibiting projection neurons. Above local neurons, a simplified depiction of a curved background manifold with a new odor that has an orthogonal component to the manifold. The circuit receives a mixture of background and new odor (apple) and outputs the new odor only.

Why do we stop smelling odors that linger? In our new @prxlife.bsky.social paper with @pfrancois.bsky.social, @gautamreddy.bsky.social, and Massimo Vergassola, we develop a manifold learning theory of this olfactory habituation process in fluctuating environments.
🔗 doi.org/10.1103/q62z...
🧵🔽

Last call for postdoctoral applications to join my group at University of Toronto. Feel free to reach out if you want to learn more about the position.

Congrats @vmochulska.bsky.social and Paul, so nice to see this story officially published! The figures look amazing!

Generative epigenetic landscapes map the topology and topography of cell fates | PNAS Epigenetic landscapes were proposed by Waddington as the central concept to describe cell fate dynamics in a locally low-dimensional space. In mode...

Very happy to share our 'Evoscape' paper, now published in PNAS ! www.pnas.org/doi/10.1073/...

Learning the principles of T cell antigen discernment T cells are central to the adaptive immune response, capable of detecting pathogenic antigens while ignoring healthy tissues with remarkable specificity and sensitivity. Quantitatively understanding h...

"Learning the principles of T cell antigen discernment" a review focused on the theoretical and experimental principles of Adaptive Kinetic Proofreading, with recent application to cancer immunotherapy ! With @fxpbourassa.bsky.social , Sooraj Achar and Grégoire Altan-Bonnet.
arxiv.org/abs/2511.18626

Merci beaucoup Paul pour la nomination, la supervision et le soutien pendant ma thèse!

As the march meeting abstract deadline approaches, please check out our session! Please RT/forward

We are hiring ! If you want to become professor of Bioinformatics in the best city of North America, check the announcement below ! Also you do need to speak French (as long as you commit to learning it :) ) www.umontreal.ca/public/www/d...

Apply now to be a CPBF Fellow in 2026! puwebp.princeton.edu/AcadHire/app...

T-cell receptors can help CAR T cells steer clear of healthy tissue while they attack tumors | Center for Cancer Research Adding a specific T-cell receptor to CAR T cells may reduce side effects of immunotherapies designed to target solid tumors.

National Cancer Institute on our venture in Cancer Immunotherapy :)

ccr.cancer.gov/news/article...

Pour une immunothérapie encore plus précise Une équipe de recherche réussit à créer une cellule immunitaire plus efficace qui combat les cancers sans toucher aux tissus sains.

"Pour une immunothérapie encore plus précise" : merci à Catherine Couturier et à UdeM Nouvelles pour la couverture de notre récent article, en collaboration avec les groupes Taylor et Altan-Bonnet au NCI ! nouvelles.umontreal.ca/article/2025...

As promised, a 'skeet' -orial on our paper published last week !

Engineering TCR-controlled fuzzy logic into CAR T cells enhances therapeutic specificity Robot-assisted analysis and theoretical modeling of TCR/CAR crosstalk enable the design of adoptive T cell therapies that maximize anti-tumor activity and minimize toxicity in healthy tissues.

Now online! Engineering TCR-controlled fuzzy logic into CAR T cells enhances therapeutic specificity

Graphical Abstract of our paper : Highlights • TCRs impact CARs across a continuum of antigens, from antagonism to enhancement • Modeling of TCR/CAR crosstalk reveals ternary fuzzy logic in dual receptor activation • Fuzzy logic produces an antagonism-enforced braking system (AEBS) in CAR T cells • AEBS CAR T cells eradicate tumors with minimal toxicity against healthy human tissue

Delighted to share our herculean, collaborative paper, published online today in Cell ! In short, we circle from data to theory back to experiments to design a new anti-cancer immunotherapy. www.cell.com/cell/fulltex...