Engineering innate immunity // Host-pathogen interactions // Systems Biology // Tuberculosis @MIT @MITDeptOfBE
Boston, MA
Joined September 2017
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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.
biorxiv.org/content/10.64898…
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.
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: biorxiv.org/content/10.64898…
Anyone in my science network have experience with producing soluble TCRs? Better yet affinity maturation of TCRs?
Anyone in the de novo minibinder design space using their binders as flow cytometry staining reagents? Would love to compare notes if so!
Happy to share our newest preprint on antigen presentation of Mtb-derived peptides on MHC-I: biorxiv.org/cgi/content/shor…
This is a follow up to our previous paper where we applied immunopeptidomics to understand MHC-I presentation by Mtb-infected cells: elifesciences.org/articles/8…
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.
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