The Discrimination of Infectious Non-Self from Noninfectious Self 
can induce the expression of co-stimulatory activ- 
ity in the latter cell. It has been known for some 
time that T cells reactive to a foreign epitope 
linked to a self protein can activate B cells that 
will produce antibody directed at the protein. 
Our studies have now shown that anti-self protein 
B cells become activated in this way so that they 
can now present the self protein in an immuno- 
genic form to self T cells, leading to a sustained 
autoimmune T cell response. We have generated 
autoreactive T lymphocytes by this means and are 
testing whether they can generate a sustained au- 
toimmune response in vivo. 
Now that the phenomenology of discrimina- 
tion of infectious non-self from noninfectious self 
has been established, and experimental systems 
put in place to characterize this response, our 
studies will begin to focus on the receptor-ligand 
pairs involved in the discrimination of infectious 
organisms from the noninfectious host. A system 
already established to detect the increase in co- 
stimulatory activity has revealed that inducers of 
co-stimulation act on virtually all antigen-present- 
ing cells. Assuming that this process operates 
through a receptor-ligand pair, the result demon- 
strates that such receptors are nonclonally distrib- 
uted, as we predicted in 1989. 
We propose that the receptors currently uti- 
lized by the immune system to discriminate in- 
fectious from noninfectious are those that once 
allowed primitive organisms to regulate their im- 
mune effector responses. Such receptors may still 
function in the early nonclonal phases of host de- 
fense, as well as in triggering the induction of 
specific clonal defense as discussed above. If this 
proves to be so, the innate and specific immune 
responses will be shown to be linked not only at 
the effector phase but also at the recognitive 
phase. Such a synthesis is the long-term goal of 
our research in this area. 
On a more practical level, identification of re- 
ceptors that regulate the induction of immunity 
may lead to up- and down-regulation of immune 
responses to achieve the desired level of effector 
function in such situations as allergy, autoimmu- 
nity, graft rejection, and cancer. 
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