A new human gene complex encoding the killer cell inhibitory receptors and related monocyte/macrophage receptors

Activation of various immune cell types can be prevented by negative signaling receptors. Natural killer (NK) cells, which can lyse tumor or virus-infected cells, express inhibitory receptors that recognise distinct 'self' class I molecules of the major histocompatibility complex [1], Recognition of self class I molecules results in a negative signal to prevent NK mediated killing of healthy cells [2]. Human and mouse NK cells express both immunoglobulin-like type I inhibitory receptors - such as the human killer cell inhibitory receptor (KIR) and the mouse gp49B glycoprotein - and lectin-like type II inhibitory receptors - such as the human CD94/NKG2 heterodimer and the mouse Ly-49 receptor family [1], These receptors use tyrosine phosphorylation motifs in their cytoplasmic tails to deliver a dominant-negative signal by recruiting the tyrosine phosphatase SHP-1 [3-5], We have identified a new family of monocyte/macrophage immunoglobulinlike receptors (MIRs) related to KIR, Two cDNA clones with sequence similarity to each other and to the gp49B gene were isolated from human lymphocytes; both encode proteins containing four immunoglobulin domains and the conserved cytoplasmic inhibitory motifs, and transcription of both was detected primarily in monocytes/macrophages, rather than T, NK, or mast cells, The MIR genes are closely linked to the KIR gene family and the gene for Fc alpha R on chromosome 19, at cytogenetic band q13.4, A mouse sequence related to MIR was mapped to a region on mouse chromosome 7 syntenic with human 19q13.4. Our findings should facilitate studies of the evolution and function of the MIR and KIR families.