Jamie Heather
@jamieheather.bsky.social
🇬🇧 immunulogist in 🇺🇸 | instructor @ MGH/HMS | TCRs and pMHC
Technically a James | ʤeɪmi hɛðə˞ | he/him
@jamimmunology in the old place
papers, tools, & 3d printed labware here: https://jamieheather.github.io/
Technically a James | ʤeɪmi hɛðə˞ | he/him
@jamimmunology in the old place
papers, tools, & 3d printed labware here: https://jamieheather.github.io/
I shudder to think at the amount of super important cells that have been sorted straight into the waste tank
November 21, 2025 at 4:21 AM
I shudder to think at the amount of super important cells that have been sorted straight into the waste tank
4) This is using naturally paired CDR3s, but shorn of framework context... so do you need pairs? Why not just mess it up, do all vs all? Intrigued to see if there's enough data to see rules about which CDR3 works where.
5) I can't wait for the de novo TCR prediction competitions to kick off!
5) I can't wait for the de novo TCR prediction competitions to kick off!
November 21, 2025 at 3:36 AM
4) This is using naturally paired CDR3s, but shorn of framework context... so do you need pairs? Why not just mess it up, do all vs all? Intrigued to see if there's enough data to see rules about which CDR3 works where.
5) I can't wait for the de novo TCR prediction competitions to kick off!
5) I can't wait for the de novo TCR prediction competitions to kick off!
3) Presumably a similar process could be used to iterate over a bunch of related pMHC variants and check for potential clashes that way? Computational X-scans of the epitope, would be huge. Similarly, could you not just use natural TCRs and iterate over a bunch of pMHC to deorphanise?
November 21, 2025 at 3:36 AM
3) Presumably a similar process could be used to iterate over a bunch of related pMHC variants and check for potential clashes that way? Computational X-scans of the epitope, would be huge. Similarly, could you not just use natural TCRs and iterate over a bunch of pMHC to deorphanise?
It's hard to say much about what they could be responding to though (as I can't seem to see what the APCs were for a lot of these expts), but I wonder if some of those are just made very HLA-bindey TCRs. However the fact they could find any specifics is remarkable.
November 21, 2025 at 3:36 AM
It's hard to say much about what they could be responding to though (as I can't seem to see what the APCs were for a lot of these expts), but I wonder if some of those are just made very HLA-bindey TCRs. However the fact they could find any specifics is remarkable.
2) Some of those off-target activation results are absolutely crackers. I mean, we always knew both that TCRs are super cross-reactive and that selection is super important, but it looks like for a lot of these TCRs just about everycell would be be catching strays...
November 21, 2025 at 3:36 AM
2) Some of those off-target activation results are absolutely crackers. I mean, we always knew both that TCRs are super cross-reactive and that selection is super important, but it looks like for a lot of these TCRs just about everycell would be be catching strays...
Wow, this is very damn cool! It's pretty dense and I'm in deadline season, so I've only given it a once-over, but a few thoughts leap to mind:
1) I'm amazed they can do all that with such modest computational demands, I would've naively presumed it'd take a lot more.
1) I'm amazed they can do all that with such modest computational demands, I would've naively presumed it'd take a lot more.
November 21, 2025 at 3:36 AM
Wow, this is very damn cool! It's pretty dense and I'm in deadline season, so I've only given it a once-over, but a few thoughts leap to mind:
1) I'm amazed they can do all that with such modest computational demands, I would've naively presumed it'd take a lot more.
1) I'm amazed they can do all that with such modest computational demands, I would've naively presumed it'd take a lot more.
Or worse, the classic "we did this as previously reported in [X]", which did it as previously reported in [Y], which adapted it from [Z], which isn't available anywhere, and when you finally track it down it turns out they didn't do anything like the method you're looking for
October 31, 2025 at 7:20 PM
Or worse, the classic "we did this as previously reported in [X]", which did it as previously reported in [Y], which adapted it from [Z], which isn't available anywhere, and when you finally track it down it turns out they didn't do anything like the method you're looking for
Absolutely, a beautiful demonstration of an incredible effect.
(It also of course suggests a very easy translational intervention to get better responses - simply treat your patients in the future when the drug regimes are better!)
(It also of course suggests a very easy translational intervention to get better responses - simply treat your patients in the future when the drug regimes are better!)
October 30, 2025 at 6:36 PM
Absolutely, a beautiful demonstration of an incredible effect.
(It also of course suggests a very easy translational intervention to get better responses - simply treat your patients in the future when the drug regimes are better!)
(It also of course suggests a very easy translational intervention to get better responses - simply treat your patients in the future when the drug regimes are better!)
Got it, labelling all my boxes 'Oct 2007' right now 👌
October 30, 2025 at 1:12 PM
Got it, labelling all my boxes 'Oct 2007' right now 👌