molecules (MHC Class I and MHC Class II) with different tissue dis$

Ian A. York york at mbcrr.dfci.harvard.edu
Wed Sep 28 11:39:13 EST 1994


	[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 
> whole.  
> 
> 
[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?

[To which I in turn reply - ]

That's a somewhat more difficult question.  Clearly class I and class II 
can coexist on the same cell - macrophages and B cells have both.  
However, I think the explanation is that the target cells for class I are 
passive - they are done upon by the CTL.  In contrast in a class II 
interaction the presenting cell is an active partner as a rule (cytokine 
release etc.)  This implies a degree of specialization of the cell.  Joe 
Somatic Cell is already specialized for some function and it is more 
energy efficient to have specialized survey cells do the class II work.  
These cells can also be more phagocytic than are general somatic cells.  
A number of labs have shown that, in vitro, transfecting in class II 
proteins can turn ordinary cells into class II APCs - it's been done with 
fibroblasts, COS, and L cells that I know of - but the ability to present 
in vitro to a specific APC doesn't mean that these cell lines would be 
either functional or useful, or perhaps actively harmful (tolerogenic?) 
in vivo.

Hope this helps.

Ian

-- 
Ian York   (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-4328     Fax  (617)-632-2627




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