A novel recognition system for MHC class I molecules constituted by PIR.

The paired immunoglobulin (Ig)-like receptors (PIRs) represent a typical receptor pair of the Ig-like receptor family in which various combinations of ligand-receptor interaction provide a positive and negative regulation of immune cells, thus enabling those cells to respond properly to extrinsic stimuli. Activating PIR-A and inhibitory PIR-B are expressed in a wide range of cells in the murine immune system, such as B cells, mast cells, macrophages, and dendritic cells, mostly in a pair-wise fashion. PIRs bind to MHC class I molecules expressed ubiquitously on hematopoietic as well as nonhematopoietic cells. The unbalanced binding of PIR-A and PIR-B to MHC class I molecules may lead to the perturbation of cell development, regulation, and function as observed in PIR-B-deficient mice. Thus, PIR-A and PIR-B are indispensable for the regulation of cellular signaling and important for homeostasis of the immune system.