Explain (A) how the ligand for CD94:NKG2A serves as an indicator of non-infectious or non-malignant states of potential target cells, and (B) the consequence if ligand expression is compromised on target cells

Question

What will be an ideal response?

Answer 1

A. The ligand for the inhibitory receptor CD94:NKG2A on NK cells is HLA-E, a conserved HLA class I molecule. In common with HLA-A, -B, and -C, HLA-E must acquire a peptide in the lumen of the endoplasmic reticulum (ER) if it is to exit from the ER and progress to the surface of the target cell. Unlike HLA-A, -B, and -C, however, HLA-E is only able to bind to peptides generated from the leader sequence of HLA-A, -B, or -C after its removal from these MHC molecules. Uninfected and non-cancerous cells express adequate levels of MHC molecules and a steady supply of leader-sequence peptides ensures that normal levels of HLA-E arrive at the cell surface. This serves as an indicator of good health.
B. If a cell is infected or malignant, the levels of HLA class I molecules are decreased. This interrupts the supply of leader-sequence peptides, and thereby also causes a decrease in HLA-E on the cell surface. In the absence of ligand, NK cells bearing CD94:NKG2A are then unable to engage their inhibitory receptors; the signals from the activating receptors mobilize the killing mechanism, leading to the elimination of the unhealthy cell.