The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity

The non‐classical major histocompatibility complex (MHC) class I molecule human leucocyte antigen (HLA)‐E is the least polymorphic of all the MHC class I molecules and acts as a ligand for receptors of both the innate and the adaptive immune systems. The recognition of self‐peptides complexed to HLA‐E by the CD94‐NKG2A receptor expressed by natural killer (NK) cells represents a crucial checkpoint for immune surveillance by NK cells. However, HLA‐E can also be recognised by the T‐cell receptor expressed by αβ CD8 T cells and therefore can play a role in the adaptive immune response to invading pathogens. The recent resolution of HLA‐E in complex with both innate and adaptive ligands has provided insight into the dual role of this molecule in immunity.