molecules (MHC Class I and MHC Class II) with different tissue dis$
w95_cook at msdisk.wustl.edu
w95_cook at msdisk.wustl.edu
Tue Oct 4 09:38:48 EST 1994
In a previous article, mrc7 at cus.cam.ac.uk (Dr M.R. Clark) wrote:
>In article <36c67hINN29c at early-bird.think.com>,
>Ian A. York <york at mbcrr.dfci.harvard.edu> wrote:
>> [Ephraim asked about tissue distribution of MHC class I and II
>>molecules and Ian replied -]
>>> Ephraim, this is due to the completely different functions of the MHC
>>> molecules. Since MHC class I scan the intracellular mileau for viruses
>>> or other intracellular parasites, which can hit most cell types, they
>>> need to be on most cell types. The class II molecules scan extracellular
>>> media, so they are, in a sense, linked to anything else in contact with
>>> the extracellular medium (with distance limits, of course). Therefore
>>> they can occur on intermittent cell types and still check the body as a
>>[To which Ephraim replied]
>>Thank you for your reply. However, it begs the question of why not have
>>one class of MHC molecule that presents both endogenous and exogenous
>>antigens and which is expressed by all cells of the body? Why should MHC
>>Class II be constitutively expressed by some cells (dendritic cells, B
>>cells, thymic epithelium) but be inducible on nearly all others?
>Well an obvious reason not to have one type of MHC which presents both
>endogenous and exogenous antigens is that the T-cell recognising the
>MHC+peptide wouldn't be able to tell whether the antigen was exogenous or
>Or am I missing something in your question? :-)
I think you're on the wrong track here. T cells don't discriminate peptides
as being endogenous or exogenous. They discriminate self from non-self, but
even that is maintained through tolerance induction and does not strictly
depend on which MHC molecule is involved in binding.
I think a better explanation for why two MHC molecules exist is to allow
for a separation of CD4 cytokine responses from CD8 cytotoxic responses.
The induction of a primary CD8 response is thought to be largely helper-
dependent (although still somewhat contraversial). Allowing class I
molecules on every cell to interact with CD8's allows these cells to serve
as effective targets for previously primed T's. However, the lack of class II
means that most cell types can't induce a primary response on their own.
Therefore when a naive CD8 encounters a self antigen it's not tolerant
to, no autoimmune response occurs due to lack of help. The recruitment
of "portable class II" in the form of monocytes/macrophages to a site
of inflammation allows for induction of a primary response, but only
where nonspecific inflamation is already occuring.
The inducible expression of class II on other cell types is somewhat
more confusing. It's not clear that the expression of class II in the
absence of costimulators accomplishes much of anything. I believe the
current thinking is that induction of class II on endothelium serves an
effective role in homing activated T's to sites of inflammation. Class II
expression on other cell types, tho, does not seem to serve any clear
purpose as far as I know.
Hope this helps!!
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