Ultimately, most methods for doing immunopeptidomics are intrinsically flawed (stupid) because you're often introducing these completely fictitious (stupid) situations to produce lots and lots of peptides.
You grow funny cells that overexpress the few classes of HLAs that those (crappy and haven't notably improved in enrichment or discriminatory power in over a decade) antibodies can pull down. And/or you take your cells and you grow 4,000 gallons of it and cross your fingers and hope that you still maintain the same surface peptide expression.
The real goal of almost all immunopeptidomics is to take a single biopsy from a cancer, find that it has some very specific signature on it and then rain all the hellfire of modern medicine down on that cell type. CAR-T or bispecific antibodies or super charged poison warheads fused to antibodies.
But we've never ever had enough material for that. We've had to do the other (stupid) things.
But...all the sudden sample prep, HPLCs, and high res mass specs are all scrambling for more and more sensitivity so that we can go out and say "look at how many proteins I can count in a single cell!"
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