In article <1995May16.135540.1 at ania.path.ox.ac.uk>, macpherson at molbiol.ox.ac.uk
writes:
>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
When you feed OVA or KLH to these rats, are the DC cells the only antigen
presenting cells involoved or could perhaps another APC (for instance B cells)
also present the antigen? If this is true could then the non-DC APC be
responsible for inducing tolerance and the DC would not require a 'danger'
signal?
Chris Thobur
