Self/nonself discrimination

plas_d at plas_d at
Tue Jul 19 15:45:11 EST 1994

Don Forsdyke wrote:
>Does an antigen-presenting cell take in antigens randomly? Surely, an
>antigen has first to be labelled as "foreign" by reacting with an antibody
>(either free or cell-bound)? The pre-existing repertoire of antibodies
>then determines which antigens will be taken up. The antibody repertoire is not>random, so why should antigen-uptake be random?

I would like to address the statement concerning the antibody repertoire.
I feel that the antibody repertoire does have a degree of randomness to it,
due to the effects of somatic hypermutation and inaccurate splicing
of V to D to J regions.  In theory, the immune system can generate
specific antibody to any antigen -- so long as the randomizing mechansisms
of somatic hypermutation and inaccurate splicing are allowed to
compete for antigen (the process of affinity maturation).

True, in a given individual the antibody repertoire is not completely
random.  B-cells producing self-reactive antibodies are removed,
and thus foreign antigens that are very similar to self antigens would
not be recognized by the host antibody repertoire.  This means that the
repertoire is not completely random, since undesirable elements have
been removed.  However, it may not be truly accurate to say that the
repertoire is not random.  Maybe the best term for it would be to
say that the process of developing the repertoire is random, while
the final product of this process is random
"minus" the undesirable parts.

Just a few thoughts for you all to consider.  I am interested in
you feedback.


Dave Plas
{No permanent address yet}

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