Hominids for Clinical Trials--The Paper

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

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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.

Thanks, ewen