Class I molecules of the major histo-compatibility complex (MHC) are polymorphic glycoproteins which, under normal circumstances, are expressed on the surface of almost every cell in the body. Upon viral infection or in tumour cells, however, MHC class I can be downreg-ulated, and its absence is 'sensed' by natural killer (NK) cells in a process known as recognition of 'missing self'. This is mediated by cell-surface receptors which, on binding class I molecules, transduce inhibitory signals that block NK-cell-mediated lysis. When class I expression is lost or reduced, NK cells are released from inhibition and can, therefore, rapidly identify and eliminate virally infected or tumour cells.
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