Human natural killer cell inhibitory receptors bind to HLA class I molecules

Abstract

To obtain direct evidence that human natural killer cell (NK) inhibitory receptors physically interact with polymorphic determinants of major histocompatibility complex class I molecules, a receptor termed NK-associated transcript-2 has been produced as a soluble fusion protein with the human IgG1 Fc portion. This soluble receptor binds specifically to HLA-C alleles with serine 77 and asparagine 80 in cell adhesion assays.

Killer immunoglobulin-like receptors

“…In addition to the originally identified HLA-C specific KIRs with two Ig-like domains, KIRs characterised by three Ig-like domains specific for a group of HLA-B alleles (HLA-Bw4 supertypic specificity) or for certain HLA-A alleles (HLA-A3, HLA-A11) were subsequently identified [37][38][39][40]. Moreover, the existence of activating forms of KIR [41] lacking ITIM motifs in the cytoplasmic tail was documented [42,43].…”

The double life of NK receptors: stimulation or co-stimulation?

“…Stimulatory KIRs have counterpart receptors that, upon ligand recognition, prevent NK-cell activation. KIRs with inhibitory activity recognize ubiquitously distributed MHC class I molecules [42][43][44]; stimulatory KIRs might bind the same ligands, albeit with reduced affinities, or different ligands entirely [45,46]. It is possible that stimulatory KIRs, as has been observed for inhibitory KIRs, bind with higher affinity to MHC class I complexes presenting specific peptides [47,48].…”

Anatomy of a murder—signal transduction pathways leading to activation of natural killer cells

“…This fits well with the implication of NK cells in anti-tumour and anti-viral defence, because infected or transformed cells usually down-regulate the expression of MHC class I molecules. This hypothesis has been subsequently reinforced by the description of inhibitory receptors capable of binding MHC class I molecules [9][10][11]. However, NK cells are also able to kill target cells that express high levels of MHC class I, providing that the target expresses ligands for activating receptors [12].…”