A month or so ago, I posted a question about carbohydrates and
proliferation, and got a number of interesting responses, one of which
mentioned the recent Nature paper, Bezouska, et al. "Oligosaccharide
ligands for NKR-P1 protein activate NK cells and cytotoxicity." We
discussed that paper in a lab journal club, and had some difficulties with
it, probably because we're not glycobiologists by training.
The paper shows that the NKR-P1 natural killer cell receptor binds
to a huge number of oligosaccharide ligands, from small to large, sufated,
fucosylated, sialylated, phosphorylated--you name it. Does anyone have any
thoughts on how the NKR-P1 can bind so many different ligands? (One of my
colleagues kept asking, "so what's the bottom line here?") Does this
receptor have multiple ligand-binding domains, i.e., other domains in
addition to the CRD that was found by homology to CRD's in other lectins?
However, the paper also shows that the binding to certain ligands,
specifically certain forms of heparin sulfate, is much, much higher (up to
10,000 fold ?!) than the binding to other oligosaccharides like HNK1. So,
would the binding to the non-sulfated oligosaccharides be "meaningful" in
vivo, since it's so much lower affinity than the binding to chondroitin-
and heparin-sulfate ligands?
And, how realistic is the proposal to purge tumor or virally
infected cells using oligosaccharide-ligand-containing liposomes? How
would one target the liposomes to the tumor? Wouldn't they just go
everywhere, resulting in a generalized (and rather nasty) natural killer
cell response to both normal and abnormal tissues? On the other hand, if
it worked, it sounds like it could be really cool.
Responses to email in addition to public posts would be much
appreciated. My other purpose in posting is to see if I will get any
traffic on bionet.glycosci; I am still having no luck with it, despite
repeated emails to my local administrator, and to bionet-help.
Sincerely,
Karen Allendoerfer
Karen L. Allendoerfer, Ph.D. Division of Biology
ravena at cco.caltech.edu 216-76 Caltech
Pasadena,
CA 91125 USA
(818) 395-6827
Any views expressed are solely my own and do not necessarily reflect those
of Caltech or its employees.
