JC? Sort of. CTL assay question, and more.
Shiv A. Prasad MicroBio
shiv at hiv.med.umn.edu
Thu Sep 15 16:25:49 EST 1994
In article <3579tn$7k4 at nntp.Stanford.EDU> ladasky at leland.Stanford.EDU (John Ladasky) writes:
> I just finished a presentation of the paper "Cytotoxic T cell
>memory without antigen" (Lau LL et. al., Nature 369:348, 23 June 1994)
>for a face-to-face journal club here at Stanford. The authors claim
>that they have demonstrated the existence of a memory T cell population
>specific for lymphocytic choriomeningitis virus (LCMV) that can be
>adoptively transfered from one host to another.
>1) A technical quibble: the authors claim to have an in vitro CTL
> stimulation assay in which "virgin T cells do not generate an anti-
> viral response." This comment is unreferenced. It's important
> that this is true, because they use limiting dilution assays to
> measure the fraction of CTL precursors (presumably memory cells) in
> their animals, and there's typically a 100-fold excess of "normal"
> CD8+ cells in their assay. I read several papers referenced by this
I can't find my copy of this paper, but here are my thoughts from what I
remember. The frequency of anti-LCMV CTL in a naive animal should be on
the order of 1:100,000 or so, and the frequency that Lau et al. found in
the recipient mice was significantly higher, and remained at a higher
frequency than one would expect in a naive mouse. That would argue against
the memory effect being due to naive anti-LCMV CTL.
>2) The authors work pretty hard to prove that they have not transfered
> LCMV along with their T cells. Yet previous studies, in which whole
> spleens were adoptively transfered into mice (thereby increasing the
> chance of transfering a few antigen-presenting cells along with the
> CTL's), failed to show long-term memory. Another difference in the
I think that Rafi Ahmed argues that this is a big difference between his
group's work and the Zinkernagel group. The different results may be a
result of the cell types transferred. Perhaps the transfer of APC with
the memory cells allows peripheral deletion of those memory cells.
> whole virus. In a review article (Matzinger PJ, Nature, same issue
> as the Lau article, pp. 605), it's suggested that "The complex
> structures of... LCMV... offer a greater probability of cross-reac-
> tions with environmental antigens." Personally, I don't buy this
> argument. There are only a couple of peptides from LCMV that are
> strongly immunogenic.
I don't buy that environmental x-reactivity either. In fact the accompanying
paper shows that memory persists when donor "memory" cells are transferred
into beta-2 microglobulin knockout mice, so there is less chance of TCR
occupancy on the donor cells, unless they present to themselves.
>Unique ID : Ladasky, John Joseph Jr.
shiv at lenti.med.umn.edu
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