In article <jcherwon.50.000FFB3F at dres.dnd.ca>, jcherwon at dres.dnd.ca (John Cherwonogrodzky) writes:
> Dear Colleagues:
> I'm a bacteriologist, not an immunologist, and found this topic
> of discussion fascinating. I recall that several years ago I read where,
> instead of my perception that proteins are digested and broken down into basic
> amino acids, there was a report that large components, if not the whole
> protein, got into the blood stream. Is this true?
> It struck me that if a protein gets into the blood stream by the
> intestinal tract and is tolerated whereas if it is directly injected it may
> cause an immune response (anaphylaxis), then there must be some "book-keeping"
> (labelling , glycosylation, processing, conformational changes) going on to
> identify the method of entry.
> Comments?....John
John, Undoubtedly whole proteins can get into the blood from the gut in small
amounts and do not seem to be immunogenic, but, if soluble proteins, carefully
freed from complexes, aggregates and denatured molecules are injected IV, they
are often tolerogenic, despite peptides from them being present as immunogenic
complexes with MHC on spenic dendritic cells (Inaba & Steinman). Similarly,
we have shown that after feeding OVA or KLH to rats, DC in the intestinal wall
acquire antigen-derived peptides and can present them to sensitized T cells
"in vitro" and can sensitize naive T cells "in vivo" (Liu & MacPherson). We
have always puzzled about this anomaly of mature, immunostimulatory DC
expressing antigenic peptides but not causing sensitization, and this is where
Polly Matzinger's ideas make sense - if the DC require some extra "danger"
signal to enable them to activate a resting T cell, all is well (our "in
vitro" manipulations of DC may be all that is required to "activate" them).
We do not however have any idea what activation of a DC means! Our
lymph-borne DC express high levels of B7 when we collect them.
Gordon MacPherson
macpherson at molbiol.ox.ac.uk
