Tolerance: cell receptors

Fri Jul 16 08:32:39 EST 1993

  Has anyone noticed the subtle reevaluation of quantitative aspects of
lymphocyte signalling recently?-of some relevence to the hypothesis that
tolerance is some function of the number of determinant-receptor reactions at
the cell surface:

  (i) Williams and Beyers. Nature 356, 746-747 state: "It is generally
thought that TCRs must be crosslinked to activate a T cell, yet how is
this to occur through the TCR:MHCpep interaction? It seems most
improbable that adjacent MHC molecules will display the same peptides,
and to give a cross-linking signal two MHC molecules displaying the same
peptide would have to be tethered together."

 (ii)Tamura and Nariuchi. J. Immunology 148, 2370-2377 state: "These
results indicate that monovalent anti-CD3 is more efficient than divalent
anti-CD3 in induction of IL2 production and that cross-linkage of the
TCR/CD3 complex is not necessarily required for T cell clone activation."

(iii)Ucker, Meyers and Obermiller J. Immunology 149, 1583-1592 state:
"At low stimulatory dose [of antigen], cells do not respond but they
remain viable for extended periods. At higher dose (operationally in the
normal range), cells proliferate in a dose-dependent fashion. Finally,
at still higher dose, proliferation is inhibited and cells rapidly
become non-viable." [i.e. tolerant].

                         Don Forsdyke (Discussion leader; Bionet.immunology

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