'Nonspecific' MHC-unrestricted killer cells and their receptors

The receptors involved in apparently nonspecific, MHC- unrestricted effector cell-target cell interaction and lysis continue to raise controversy. They bind to distinct ligands on their target cells and activate diverse cellular functions such as gene expression, lymphokine production, proliferation and/or cytolytic activity by the effector cells. Several distinct receptors may mediate MHC-unrestricted cytotoxicity. Here, Peter Hersey and Reinder Bolhuis review evidence that the four main receptors involved in triggering this form of lytic activity are the CD2 molecule (the sheep red cell receptor), CD3-associated αβ chain T-cell receptor (TCR), the γδ chain TCR-CD3 complex and the CD16 molecule (the IgG0Fc receptor). The apparent non-specificity specificity of killing is a reflection of the widespread expression of natural ligands for these receptors on target cells.