Self/Not-self discrimination (YORK)

[Greg Appleyard]

I have two comments and a question. First, very early in this discussion, 
there seemed to be some confusion as to which cells were discriminating 
between self and non-self. I think the comments of YORK make it clear that
the cells presenting the antigens do not perform this function although, as the 
previous article suggested, the APC may be signalled to bias peptide 
incorporation into MHC I. T-cells discriminate between self and non-self, 
not the APC. 
 

: 	It is my expectation that these non-clonal mechanisms will predate the
: adaptive immune system, and thus the self/non-self discrimination
: mechanisms required by the adaptive immune system will have evolved against
: a background in which both the activation of the immune system and the
: definition of self are conditioned by the presence of pathogens.

My second comment is that it would be my expectation that non-clonal 
mechanisms of defence and thus self/non-self discrimination evolved much 
earlier and not in response to the presence of pathogens but rather  in 
response to a need to defend territory (as in the case of sponges and 
corals) and that the seeds of self/non-self discrimination began with 
the identification of particles ingested for food (as in the case of 
amebas and starfish larvea). Evolving to recognize pathogens may have come 
somewhat latter.  

My question is, since T-cells do the self/non-self discrimination and 
such discrimination is made vigilent against intracellular infections 
through thymic education, how is it that self-specific T-cells exist 
normally in the periphery without rampant autoimmunity. The self-specific 
T-cells must be regulated, but how? It seems a paradox that self/non-self 
discrimination is made on the basis of selecting T-cells without 
self-reactivity (negative selection) and yet self-specific T-cells are 
part of the normal lymphocyte repertoire.

Greg Appleyard
Dept. Vet.Micro.Immunol.
University of Guelph
Canada