MHC-I viral Ag presentation

Kenneth Frauwirth frauwirt at OCF.Berkeley.EDU
Thu May 7 15:00:20 EST 1998

In article < 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 "BioKen" Frauwirth
Gwen Knapp Center for Lupus and Immunology Research
University of Chicago

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