The CD94/NKG2A heterodimer is an inhibitory receptor expressed by CD8+ CTL and NK cells that, upon activation by HLA-E, downregulates their cytolytic activity against tumour cells. NK inhibitory receptors share a common regulatory sequence of amino acids in their cytoplasmic tails, the immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Human NKG2A has two ITIMs which contain tyrosine residues that are phosphorylated, presumably by a src tyrosine kinase, following interaction of CD94/NKG2A with HLA-E expressed on target cells. The phosphorylated ITIMs can recruit and activate the phosphatase Src homology 2 domain-bearing tyrosine phosphatase-1 (SHP-1), which suppresses the signal generated from cell surface-activating receptors.
Pace E, et al. Altered CD94/NKG2A and perforin expression reduce the cytotoxic activity in malignant pleural effusions[J]. European Journal of Cancer, 2011, 47(2): 296-304.