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Ian

The concept is such a simple one that (in retrospect) I'm surprised we haven't seen it used before. It is a brute-force approach to generating a broadly-diverse T cell response. It lacks some elegance but who cars about elegance, if it works.

The use of 15mers is a little interesting. Though this is standard technique for stimulating CTL, 15mers are well above the optimum size for CTL recognition (they want to see 9- or 10mers). The advantage of 15mers, of course, is that you don't need as many; you can span the proteome with fewer 15mers than 10mers. It's believed (and has been shown in some cases) that the stimulation in this case comes not from the 15mers but from very small amount of contamination with shorter peptides. Here they used peptides that were >80% pure, and probably much of the remaining <20% encompass the range of shorter nested peptides within that. Using 10mers or 9mers might even induce better responses for CTL. (Or it might be worse, for various reasons.)

The other advantage of 15mers is that this is close to optimium size for CD4 responses, so they can trigger both forms of resposne with the same set of peptides.

There are still a lot of issues to resolve, but it's new and exciting direction.

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