In article <3.0.32.19980507114532.006ecd80 at darwin.bio.uci.edu>,
Victor DeFilippis <vrdefili at DARWIN.BIO.UCI.EDU> wrote:
>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?
There is nothing wrong with your scenario, but there appears to be a
mechanism (or mechanisms) for a subset of professional APC to present
exogenously derived antigens on Class I molecules. One manifestation of
this phenomenon is "cross-priming": a tumor cell of haplotype A is used to
immunize a mouse of haplotype B. CTL recognizing tumor-specific antigens
on *both* haplotypes can be found. This can happen in one of two (non-
exclusive) ways: (1) processed peptides from a non-professional APC are
transferred to the MHC molecules of a professional APC (as with the heat
shock proteins studies of Srivastiva), or (2) professional APC take up
intact or partially processed antigens, process them, and present them on
Class I (as shown by the labs of Ken Rock and Cliff Harding). Another lab
which has done a lot of work on cross-priming is that of Hy Levitsky.
I hope that answers some of your questions,
Ken
--
Ken "BioKen" Frauwirth
Gwen Knapp Center for Lupus and Immunology Research
University of Chicago
http://www.ocf.berkeley.edu/~frauwirt
