NK cell-mediated killing?

Ian A. York iayork at panix.com
Thu Dec 28 10:03:12 EST 2000

In article <p05010407b66ff0e2e1ef@[]>,
Klaus D. Elgert <kdelgert at vt.edu> wrote:
>scenario, what is the mechanism by which NK cells distinguish class I 
>MHC carrying self-peptides from class I MHC carrying viral derived 
>peptides?  In particular, if the virally infected target cell's 

Probably they do not so distinguish.  Viral peptides are just as good as 
self peptides, as far as the NK cell is concerned.  (There are a handful 
of papers that suggest that some NK cells, under some circumstances, are 
peptide-sensitive; but they're a distinct minority.)

>signal?  Or do NK cells only kill virally infected cells that have 
>altered class I MHC molecules or reduced (or inhibited) expression of 
>class I MHC molecules?  If the answer to the last question were yes, 

(The answer to that question is yes.)

>then it would be wrong to say, at least in a generic way, that all 
>cells infected by virus activate NK cells?  The flipside would be 

There's another point you need to remember.  MHC class I delivers an
inhibitory signal.  But NK cells *also* need an activation signal, and the
decision to lyse or not lyse depends on the balance between positive and
negative signals.  Most cells have a certain (low) level of positive,
activation signals; the normal level of MHC expression delivers sufficient 
negative signal that the gestalt the NK ccell receives is negative:  Do 
not lyse this cell.  In cells with low MHC expression, the normal levels 
of positive signals are sufficient to overcome the (now reduced) negative 
signal, and the NK cell can lyse the target.  But even if the MHC class I 
is relatively normal, it is possible for the positive signals to also be 
overexpressed, higher than the constitutive levels, and the NK cell will 
still lyse these cells even in the presence of normal MHC expression.  
(But it's easiest to lyse cells with low MHC.)

>that all virus-infected cells must have either altered (does every 
>molecule have to be changed?) and/or reduced or inhibited expression 

NK cells tend to have receptors specific for subclasses of MHC, so no, not 
every molecule needs to be changed.

>virus-infected cells.  So if MHC things are "normal" on a 
>virus-infected cell, only CTLs work.  If MHC things are "abnormal" on 
>a virus-infected cell, only NK cells work.

This is the general summary, and it's reasonably accurate, but it's more 
complicated in the details.


    Ian York   (iayork at panix.com)  <http://www.panix.com/~iayork/>
    "-but as he was a York, I am rather inclined to suppose him a
     very respectable Man." -Jane Austen, The History of England

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