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