Mandl Lab

Huge congratulations to Dr. Connie Shen @peepingcells on delivering an outstanding thesis defense! Our fourth Mandl PhD will soon be leaving the nest, trading cold Montréal for sunny California! ☀️All the best!

Interestingly, against a chronic fungal infection 🍄that T cells can't clear, both our model and experiments agreed that this TCR diversity didn't offer any extra protection. So, it seems that these low-binding TCRs are useful for certain chronic battles!

But does TdT contribute primarily to low-reactivity T cells? We show experimentally that this is indeed the case, with TdT-deficient T cells (🔴) 1) binding viral antigens stronger, on average, and 2) clearing a chronic viral infection slower than TdT-sufficient T cells.

Our model showed that, unlike with acute infections (🟣) skewing the response toward reactive (but more readily exhausted😪) T cells, chronic infections (🟠) instead lead to a dominance of more “endurant” T cells with weaker antigen binding strengths (ie “looser” handshakes 🤝).

We hypothesized that TdT-diversified TCRs had lower antigen binding strengths (pMHC reactivity) on average, and that these T cells would specifically benefit clearance of chronic pathogens- and we started by designing a computational model to test this idea.

Our PhD student Angela @ImmuneVet co-host of the TWiV podcast with @profvrr recently interviewed @bjesseshapiro and Corinne Maurice with their students Sana Naderi and Anshul Sinha about their cool virus research going on at @mcgillu! @McGillMed 📺bit.ly/3Hb9Aet

And this work featured on the current issue cover! Amazing collaboration with @JohannesTextor @MelicharLab, and the Westermann team

In our second approach, we isolate all the neutrophils and annotate the number of lobes in each. We track these neutrophils over time and also observe that greater lobularity correlated with greater cell speed and displacement across the channels.

Across donors, we find that the segmented and hypersegmented neutrophils more readily cross the restrictive 2 μm section compared to their banded counterparts.

We test the hypothesis in a two-pronged approach. First, we sorted the neutrophils into 3 groups enriched for banded, segmented, and hypersegmented nuclei. We differentially stained these neutrophils and imaged them by live confocal microscopy.