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THE T CELL RECEPTOR AND ITS LIGANDS 
John W. Kappler, Ph.D., Investigator 
Normally an effective response by the immune 
system's T cells to the antigens of microbial invaders 
is essential to preventing and curing infection. How- 
ever, Dr. Kappler and his colleagues have discov- 
ered that for a class of microbial protein antigens 
that they call superantigens, a T cell response ap- 
pears to be detrimental to the host. The key feature 
of these special antigens is that T cells respond to 
them more frequently by many orders of magnitude 
than they do to conventional antigens. 
T cells recognize foreign antigens by means of a 
surface receptor that varies from one T cell to the 
next. The five variable components of the receptor 
are called Va, Ja, V/S, D|8, and J/3. Usually fragments 
of foreign antigens create a ligand for this receptor 
when they bind to a groove on one of the cell-bound 
products of the major histocompatibility complex 
(MHC) . The frequency of T cells responsive to this 
antigen-MHC complex is low (~0.001%), since the 
interaction requires exactly the right combination 
of the five receptor components to generate a 
match. 
T cells also recognize superantigens complexed 
to MHC molecules. But the superantigens appear to 
bind to a unique site on the MHC in such a way that 
only the V/3 portion of the T cell receptor need be of 
the correct type to generate a response. This results 
in a high frequency of responding T cells (1-1 0%) . 
The activation of so many T cells can be disastrous 
for the host because of the sudden release of power- 
ful biological mediators. Symptoms include vomit- 
ing, diarrhea, toxic shock, and even death. Dr. 
Kappler and his colleagues have been examining the 
superantigens' structural features that underlie their 
unusual properties. They have found that the mode 
of action of superantigens from different types of 
340 
