Bryson Lab

Engineering innate immunity // Host-pathogen interactions // Systems Biology // Tuberculosis @MIT @MITDeptOfBE

[Bryson Lab @TheBrysonLab]

@philippzross Thank you! Puzzle indeed!

[Bryson Lab @TheBrysonLab]

Antigen discovery and TB vax friends 🧵

We set out to find more Mtb peptides presented on MHC-I. We had a strong biological prior, a high-throughput binding screen, and a very sensitive targeted MS assay.

Of 286 candidates, we detected 2.

https://t.co/XfEeoMLWMD

[Bryson Lab @TheBrysonLab]

Caveats we’d flag ourselves: 2 hits is little to train on, and 2/6 is still a lot of misses. Antigens below our LOD (~1-10 copies/cell) may exist, though at that level it’s not obvious they’d make good targets.

Preprint: https://t.co/XfEeoMMuCb

[Bryson Lab @TheBrysonLab]

Big picture: presentation looks like a series of filters. Not TB-specific. The same logic may apply to other pathogens and to tumor antigens cross-presented by DCs.

[Bryson Lab @TheBrysonLab]

@csgarrix @jkagan1 I was thinking the same thing

[Bryson Lab @TheBrysonLab]

@BobbyHollings Wait, I love this! If you ever want to target infected cells, let’s chat!

[Bryson Lab @TheBrysonLab]

@mosasaurus27 That would be amazing, thank you!!!

[Bryson Lab @TheBrysonLab]

Anyone in my science network have experience with producing soluble TCRs? Better yet affinity maturation of TCRs?

[Bryson Lab @TheBrysonLab]

Anyone in the de novo minibinder design space using their binders as flow cytometry staining reagents? Would love to compare notes if so!

[Bryson Lab @TheBrysonLab]

Thanks to our many collaborators at the @ragoninstitute and across the broader community and our funders #tuberculosis

Congrats especially to Owen and Rachel, the two fearless graduate students who led this work -- y'all are the best <3

[Bryson Lab @TheBrysonLab]

Happy to share our newest preprint on antigen presentation of Mtb-derived peptides on MHC-I: https://t.co/T5THToFRWe

This is a follow up to our previous paper where we applied immunopeptidomics to understand MHC-I presentation by Mtb-infected cells: https://t.co/6afhcHifxp

[Bryson Lab @TheBrysonLab]

We're excited! This study supports the concept that there are multiple ways to transfer proteins from the phagosome to the cytosol, and that Mtb specifically takes advantage of this.