Overview of the Killer Cell Immunoglobulin-Like Receptor System

Abstract

Natural killer (NK) cells are more than simple killers and have been implicated in control and clearance of malignant and virally infected cells, regulation of adaptive immune responses, rejection of bone marrow transplants, and autoimmunity and the maintenance of pregnancy. Human NK cells largely use a family of germ-line encoded killer cell immunoglobulin-like receptors (KIR) to respond to the perturbations from self-HLA class I molecules present on infected, malignant, or HLA-disparate fetal or allogenic transplants. Genes encoding KIR receptors and HLA class I ligands are located on different chromosomes, and both feature extraordinary diversity in the number and type of genes. The independent segregation of KIR and HLA gene families produce diversity in the number and type of KIR-HLA gene combinations inherited in individuals, which may determine their immunity and susceptibility to diseases. This chapter provides an overview of NK cells and their unprecedented phenotypic and functional diversity within and between individuals.

Immune Abnormalities in Patients Meeting New Diagnostic Criteria for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

“…Specifically, in the ICC group profound increases were observed in KIR2DL1, KIR3DL1 and NKG2D in contrast to the 1994 CDC group. KIR2DL1 and KIR3DL1 are inhibitory receptors while NKG2D is an activating receptor, these receptors inhibit and activate NK cytotoxic activity respectively [22][23][24][25]. An increase in inhibitory receptors in the ICC group may account for the reduced cytotoxic activity.…”

The Killer Cell Ig-like Receptor 2DL4 Expression in Human Mast Cells and Its Potential Role in Breast Cancer Invasion

“…KIRs are transmembrane proteins that possess twodomain (2D) or three-domain (3D) Ig-like extracellular domains. They are expressed on human natural killer (NK) cells and recognize major histocompatibility complex (MHC) class I molecules (2). In addition, KIRs are categorized according to the presence or absence of immunoreceptor tyrosine-based inhibitory motifs (ITIM), in other words, into KIR with long (L) or short (S) cytoplasmic domains.…”

Do educated natural killer cells make the grade in treating acute myeloid leukemia?

“…2 Since HLA and KIR genes segregate independently, individuals inheriting KIR2DS1 may be further grouped according to the levels of activating HLA-C2 ligand that NK cells encounter in vivo. This is significant because KIR2DS1-expressing NK clones derived from C2/C2 donors are less able to generate cytokines or kill when compared to similar clones derived from donors that are either C1/C2 or C1/C1 (C1/X).…”