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
shiv at lenti.med.umn.edu



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