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
