Would totally blocking these be a good answer to MS though? I question that as surely the natural process is for CTL to enter the brain and clear viruses. So people with MS and CTL blocked would be susceptible to viruses in the brain.

I think it is the first (certainly I don’t remember seeing anything like it before in the literature, but I might have missed it). But I don’t think it’s that amazing, or that it implies a lot about special mechanisms. If you look at the figure I included, you can see that MHC class I is essentially only expressed on the luminal side of the endothelium, so you don’t need to invoke anything exceptional about the processing (in particular I think it doesn’t imply directed cross-presentation), because the antigen is actually going to all the MHC class I, not a special subset of it.

It certainly is striking that the MHC class I is so strongly polarized, but polarization is what, um, polarized cells like endothelal cells do. I believe there are reports of strongly polarized MHC class I expression in other cell types (endometrial, at least, and I think I’ve seen slides illustrating it during some seminars).

Do you think that this trans-presentation capability is specific to BBB cells or can all endothelial cells do it?

Interesting question. My guess would be that the extent of polarization might be unique to the BBB, but that’s just a guess.

To me, there were two or three other things about the paper that were at least as interesting as the polarized presentation. The probability that endothelial cells can do cross-presentation is one — the list of cells that can efficiently cross-present is very short. The implication that the TcR/MHC class I interaction is enough to cause lymphocyte rolling, or binding, or extravasation, is another (I would have thought it is too low-affinity to physically halt a lymphocyte, though of course it would be on top of a lot of other interactions). And of course, the clinical implications are important, too. Still, I’d also say that none of those things are not quite enough to put this in the Top-Three-Journal category. Top ten, but low half of the top ten, seems about right, and that’s about where I’d rank J Exp Med.

Do you think that this trans-presentation capability is specific to BBB cells or can all endothelial cells do it? I am not an expert, but I guess the mechanism amounts to a ‘directed cross-presentation’ by these cells, right?