Three Questions

Ephraim Fuchs ejf at welchlink.welch.jhu.edu
Thu Dec 1 00:52:14 EST 1994

Regarding question 2, which asked whether the same mechanism preventing 
autosensitization may be used by tumor cells to escape immunosurveillance:

Yes. It is now generally accepted that T cells require two signals for 
efficient activation: signal 1 is ligation of the T cell receptor for 
antigen, and signal 2 is a "costimulatory" signal delivered by the 
antigen presenting cell (APC).  This model proposes that T cell receptor 
ligation (signal 1) in the absence of an APC-derived costimulatory signal 
results in antigen-specific tolerance.  Many people believe that 
autoreactivity to many non-thymic (peripheral) tissue antigens does not 
occur because peripheral tissues display these tissues in the absence of 
costimulatory signals.  Likewise, tumor cells may express tumor specific 
antigens (specifically, peptides that are derived from mutated 
intracellular proteins and presented in the context of MHC molecules) but 
also fail to deliver costimulatory signals, thereby resulting in T cell 
tolerance to tumor specific antigens.

Ephraim Fuchs

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