Interesting question re: APC & T cell

Ian A. York york at mbcrr.dfci.harvard.edu
Fri Sep 1 15:47:47 EST 1995


In article <427pcc$39r at agate.berkeley.edu>,
Ken Frauwirth (BioKen) <frauwirt at notmendel.Berkeley.EDU> wrote:
>In article <1995Sep1.212404.1 at cc.newcastle.edu.au>,
> <mdcabl at cc.newcastle.edu.au> wrote:

>>was: after TCR engagement of the MHC/peptide, how do the APC and T cell let go?
>>And, which cell "gets" the peptide.  It was speculated that either the TCR or
>>MHC gets cleaved, maybe both... In which case, the molecules might become
>>soluble?  Anybody have an idea or want to speculate?
>
>My understanding of this interaction is that the TCR/MHC binding affinity is
>relatively low (esp. compared to antibody/antigen), so normal intercellular
>forces are sufficient to separate the two.  Almost certainly the peptide 

I'll add that the interaction between a T cell and its target is based on 
much more than TcR/MHC interactions, and is highly regulated.  The 
interaction is probably mainly due to interactions between other adhesion 
molecules, which in turn have their affinity regulated by TcR stimulation 
- that is, when the TcR is turned on, various adhesion molecules rapidly 
but temporarily up-regulate their adhesion.  See for example 

O'Rourke, A.M., B. Ybarronda, M.F. Mescher
CD8 and antigen-specific T cell adhesion cascades.
Sem. Immunol. 5: 263-270 (1993) 

Further, the TcR is generally down-regulated by contact with MHC (shown 
most convincingly for CD4 cells, but likely true as well for CD8).  One 
potential and very interesting outcome of this is discussed in - 

Valitutti S. S., Muller, M. Cella, E. Padovan, A. Lanzavecchia
Serial triggering of many T-cell receptors by a few peptide-MHC 
complexes.
Nature 375:148-151 (1995)

and 

M.M. David
Serial engagement proposed
Natuure 375:104 (1995)

There may well be more to the disengagement as well, but as Ken pointed 
out, the TcR/MHC interaction is not likely to be the most important factor.

Ian
-- 
Ian York   (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921     Fax  (617)-632-2627




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