MHC-I viral Ag presentation

Victor DeFilippis vrdefili at DARWIN.BIO.UCI.EDU
Thu May 7 13:44:27 EST 1998

Thanks to the many kind people who responded - I am very appreciative.  

I should probably clarify my inquiry to avoid looking even more foolish
than I already do.  Now, let's say hypothetically there is a virus that
only infects cells that do not present peptides using both MHC-I and MHC-II
(APCs).  CD8+ cells are needed to combat the infection by killing those
cells harboring the virus.  Before the CD8+ cells can go forth and
specifically kill those cells they need to be activated via specific TcR
binding and the proper co-stimulation.  If a CD8+ cell happens to encounter
a peripheral (infected) cell expressing MHC-I + viral (or any) peptide that
matches its TcR it will be permanently deactivated (anergic) since the
proper co-stimulatory signal does not exist.  By itself an infected
peripheral cell presenting viral Ag using its MHC-I molecules cannot
activate (arm) the specific CD8+ cell (and upon an encounter this CD8+ will
essentially never kill again).  Now, how can the proper CD8+ repertoire
become activated if they require MHC-I binding and co-stimulation from an
APC when MHC-I can only present endogenously synthesized peptides which, in
this case, do not exist since the APCs aren't infected by the virus and
only injest them (or their proteins) using phagocytosis?  Is there
something wrong with the facts in my scenario?

Thanks again...

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