In the midst of the holiday cheer, would some NK cell gurus help
clarify stuff to a macrophage person? The following questions arose
during a debate/discussion we had in a graduate immunology course.
Literature suggests that the NK cell's ability to recognize and kill
a virally infected target cell depends on the integrity and amount of
target cell surface class I MHC proteins. This integrity and amount
of surface class I MHC proteins determine whether the NK cell's
inhibitory or activating receptor signals prevail. Given that
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
amount and class I MHC molecule integrity are normal (as cells
targeted by cytotoxic T lymphocytes [CTLs]), do/can NK cells kill
this target cell? In more technical terms, if NK cells recognize
class I MHC molecules displaying self-peptides as a "no kill" ligand
would the replacement of self-peptide with viral peptide in class I
MHC molecules be enough to cause a failure to nullify the "kill"
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,
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
that all virus-infected cells must have either altered (does every
molecule have to be changed?) and/or reduced or inhibited expression
of class I MHC molecules for NK cells to recognize and kill the
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.
Thanks,
Klaus
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