NK cells selectively kill target cells that fail to express self-MHC class I molecules. This selective killing results from a balance between inhibitory NK receptors specific for MHC class I molecules and activating receptors that are still largely unknown. Isolation of molecular clones for the human killer cell inhibitory receptors (KIR) revealed that KIR consist of a family of molecules with Ig ectodomains and cytoplasmic tails of varying length. Soluble complexes of KIR and HLA-C molecules established that KIR recognizes and binds to its ligand as an autonomous receptor. A functional expression system in human NK clones demonstrated that a single KIR can provide both recognition of MHC class I and delivery of a dominant negative signal to the NK cell. Functional evidence has been obtained for a role of the tyrosine phosphatase SHP-1 in KIR-mediated inhibition. The presence of a conserved motif used to recruit and activate SHP-1 in the cytoplasmic tail of KIR and of the mouse Ly-49 inhibitory receptor (otherwise structurally unrelated to KIR) represents an interesting case of evolutionary convergence. Furthermore, the motif led to the identification of other receptors with inhibitory potential, including a type I Ig-like receptor shared by mouse mast cells and NK cells.

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 FcαR 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.

Multidrug-resistant K. pneumoniae producing OXA-48-like carbapenemase are emerging as important pathogens in Spain due to intra- and inter-hospital, clonal and non-clonal dissemination.