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Something unknowable in immunology? Simple logic?

Ken Frauwirth frauwirt at mendel.Berkeley.EDU
Sat Jan 22 21:12:43 EST 1994

In article <2hs8sg$naa at netnews.upenn.edu>, dfonseca at mail.sas.upenn.edu 
(Dina Fonseca) writes:
|> To me, this begs the crucial question:
|> Are there true peripheral antigens?
|> I mean by this, are there proteins expressed and presented in the
|> periphery, to which tolerance must be established by peripheral 
|> mechanisms? For which failure of tolerance induction would lead to
|> autoimmunity? Surely such self proteins must exist? 
|> How could tolerance to such proteins possibly be established?
Recent studies of autoimmune diseases suggest that this is exactly the
case.  Tissue-specific proteins that are not secreted into the blood or
lymph would have to induce tolerance peripherally (unless enough of the
antigen is phagocytosed from dying cells or matrix).  Proteins such as 
collagen (cartilage, bone - rheumatoid arthritis), TSH receptor (thyroid -
Graves' disease), and acetylcholine receptor (neurons, muscles -
myasthenia gravis) are all implicated in autoimmune diseases, and none
should be available to developing T cells in the thymus (collagen might
be available to developing B cells in bone marrow) for negative
selection.  But just about any tissue-specific cellular or matrix protein
would fit into the category of "peripheral antigens".  It has been
suggested, however, that part of peripheral tolerance (perhaps a large
part) is dependent on the fact that many of these proteins are probably
not normally "visible" to the immune system in the absence of tissue
damage, since they are not present in the blood or lymph.

By the way, as long as others are introducing themselves...

I am also a grad student (with quals hanging over my head).  Our lab
studies antigen processing and presentation by APC's, in both the MHC
Class I and Class II pathways.  My focus is the role of the invariant
chain in Class II antigen processing.

It is definitely good to see the recent surge in postings to this group. 
Keep up the interesting conversations!  (Not that I have anything against
antibody requests or anything, but they just aren't as much fun to read.)

Ken Frauwirth                  BBB   IIIII    OO    K  K   EEEEE   N   N
frauwirt at mendel.berkeley.edu   B  B    I     O  O   K K    E       NN  N
Dept. of Molec. & Cell Bio.    BBB     I     O  O   KK     EEEE    N N N
Immunology Division            B  B    I     O  O   K K    E       N  NN
Univ. of Cal., Berkeley        BBB   IIIII    OO    K  K   EEEEE   N   N

"Later, at Cal, Berkeley..." "Free Huey!" "Kill the pigs!" - from T-AS

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