MHC restriction questions

Donald Forsdyke forsdyke at post.queensu.ca
Wed Oct 21 10:05:28 EST 1998


Klaus D. Elgert wrote:

> "Somatic mutation does not occur in the TCR because it would be
> detrimental to generate self-specific T-cells.  Yet, we display
> self-peptides in our MHC molecules.  Why haven't we developed
> mechanisms to display only foreign peptides? Also, if somatic mutation
> can potentially lead to self-specific T-cells, shouldn't the same hold
> with B-cells?"

    A mechanism for intracellular self/not-self discrimination  will be
found in J. Biol. Systems (1995) vol 3, 273-287 "Entropy-driven protein
self-aggregation as the basis for self/not-self discrimination in the
crowded cytosol" (See also J. Theor. Biol. (1994) vol 167, 1-12).
 
> I gave the canned answers that random mutation
> of the TCR may change thymic-induced specificity leading to
> autoreactivity; there are autoreactive B cells but T cells would
> control them, polyclonal B-cell activation, etc. 

A generic model ( affinity (specificity) maturation of T and B cells)
for positive and negative selection may be found in J. Theor. Biol.
(1975) vol 52, 187-198.

>  Also, "why not display ONLY foreign peptides?"  

That is what the J. Biol.Sys. paper addresses. For a brief update see
Cell Stress and Chaperones (1998) vol. 3, suppliment 1, page 3.

Sincerely, 
Donald Forsdyke (Discussion Leader. Bionet.immunology)



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