Self vs non-self (EJF and DRF)

Shahram Mori smori at nmsu.edu
Sun Jul 24 23:06:12 EST 1994


FORSDYKE at QUCDN.QueensU.CA wrote:
: Date:         Wed, 20 Jul 94 11:09:45 EDT
: From:         Don Forsdyke <FORSDYKE at QUCDN.QueensU.CA>
: Subject:      Re: Self/nonself discrimination
: To:           Ephraim Fuchs <ejf at welchlink.welch.jhu.edu>
: In-Reply-To:  Your message of Wed, 20 Jul 94 00:22:44 EDT
: ========================================================================
: Dr. Fuchs has agreed that the following exchange should be posted on his
: behalf:

: EJF:
: I have a couple of problems with explanations of self/nonself discrimination
: that state that only those antigens that are picked up in the form of Ag-Ab
: complexes are presented.

: 1) There is strong evidence that dendritic cells, which do not express Fc
: receptors, are the principal antigen presenting cells for naive T cells in
: vivo.  They do not usually capture antigens in the form of antigen-antibody
: complexes.  Rather, as immature dendritic cells they are able to capture
: soluble antigens as efficiently as antigen-specific B cells (see Salusso and
: Lanzavecchia, JEM, April 1994).  Therefore, I do not see how they could
: discriminate self from nonself on the basis of differential antigen capture.

: DF: Correct. If a cell has NO Fc receptors and does NOT take up Ag-Ab complexes
: then there is no basis for differential antigen capture based on recognition by
: antibody. There is NO other GENERAL basis for extracellular recognition of
: not-self. Thus, if it is true that the cell does discriminate, it must be
		  ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
: intracellularly. For a proposed basis of intracellular self/not-self discrim
  ^^^^^^^^^^^^^^^
: ination see Forsdyke 1994 (J.Theor.Biol. 167, 7-12).

What I don't understand is why  we assume that there is cell
discrimination of  antigens. Why is it necessary? All antigens self and
non-self are picked up, processed and presented. The last thing being that
there are no TCR's that recognize the self antigen, i.e. the antigen is
presented to nobody or presented to anergic T-cells. 
Wouldn't an efficient form of self tolerance be at the T and B cell level,
rather than discrmination at the extra/intracellular level?
I haven't read your paper Don, But I will for sure. :)
: EJF:
: 2) Even if the only antigens that are presented are those that first bound
: antibody, then how do the B cells that make the antibody discriminate self from
: nonself?  That is, how do you ensure that only anti-nonself antibody is around
: to bind antigen?  A two signal model would say that signal 2 for B cells is
: delivered by an antigen-specific T cell, but then we are back to the problem
: of how the T cell discriminates self from nonself.
If the Repetoir of T and B cells has been decided during the development,
then what is left over? Non-self reacting T and B cells. During
development, the autoreactive B and T cells arise and we can assume that
many do. When they come into contact with self antigen, the signal for
apoptosis results in deletion or anergization of these clones. Just by the
simple assumption that if you remove the cells that are autoreactive, then
the only thing that is left is the non-reactive Lymphocytes. 

:       Sincerely,  Don Forsdyke
:                   Discussion Leader. Bionet.immunology

cheers,

-- 
Shahram Mori					   _/\_
Program in Molecular Biology			  _\  /_
Dept. of chemistry and Biochemistry Box 3C	  \_  _/
NMSU  Las Cruces NM				    ||



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