A few days ago I explained how an evolutionary change in our hominid ancestors could explain a spectacular surprise failure of a clinical drug trial. At last, I see that the paper is now online
Thanks for the link. I found the paper really interesting, but I’m not completely convinced that Siglics explain the discrepancies between chimp and human T cell responses.
To stimulate the T-cells in vitro, they treated the cells with immobialized (meaning bound to the culture dish) anti-CD3 antibody and soluble anti-CD28 to mimic T cell receptor and accessory molecule recognition normally provided by an antigen presenting cell.
CD3/CD28 antibody treatment is certainly more physiologic than using PHA, but it still involves binding CD3 and CD28 with antibodies, not their natural ligands. Is it possible that Siglic-5 expressed on transfected human T cells bound the soluble CD28 antibody, thus depriving the T-cells of a necessary second activation signal? I’m sure their reviewers asked that question.
Also it would have been interesting to see if knocking down Siglics on the surface of chimp T-cells makes them easier to activate. I think that data would be a lot more convincing than the overexpression data they presented.
The idea that a lack Siglics contribute to humans’ susceptibility to disease is certainly interesting, and I look forward to subsequent work on this topic, especially the evolutionary basis for loss of Siglics.
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Okay–after some technical difficulties I won’t bore you by recounting, I have an announcement. For the…
Really, it’s not like I’ve discovered a new element or anything. See you tomorrow.
…to spill beans. Any minute now, honest.
…at 5 today. [That’s 5 pm EST–sorry for the confusion.]
[Hint…I’ve turned off the comments till then.]
I’m sure you’d like to pretend that you have nothing in common with a tapeworm.