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

Abstract

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.

Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

“…Genética, estructural y funcionalmente, la familia ILT está estrechamente relacionada con la familia de KIR (Natural Killer Immunoglobulin-like Receptors) (54,55), pues ambos están codificados en la región cromosómica 19q13.4 humana, conocida como el complejo del receptor de leucocitos, donde también se encuentran algunos genes para los receptores Fc de inmunoglobulinas y lectinas de tipo inmunoglobulinas que se unen al acido siálico (56).…”

LILRA2 Activation Inhibits Dendritic Cell Differentiation and Antigen Presentation to T Cells

“…From the study of leprosy in humans, we have gained insight into the immunoregulatory role of leukocyte Ig-like receptor (LILR) family (7)(8)(9) of genes (10). LILRs are expressed on lymphocytes and myelomonocytic cells, including macrophages, mast cells, and dendritic cells (11)(12)(13) and are known to regulate both innate and adaptive immune responses (14).…”

FcαRI (CD89) Alleles Determine the Proinflammatory Potential of Serum IgA

“…The gene encoding human Fc␣RI is located in the leukocyte receptor cluster on human chromosome 19q13.4 along with NK cell inhibitory receptors and leukocyte Ig-like receptors (8,9). The Fc␣RI gene consists of five exons and spans ϳ12 kilobases.…”

“…Fc␣RI shares sequence similarity with the leukocyte Ig-like receptors, killer inhibitory receptors, and other members of the leukocyte receptor cluster (8,9). Unlike the classical low affinity Fc␥RIII and high affinity Fc RI, which bind their ligands via the membrane proximal EC Ig-like domain (EC2) and form 1:1 receptor:Fc complexes through interactions with hinge-proximal Fc regions (18,19), Fc␣RI has its ligand binding site on the membrane distal EC1 domain and forms a 2:1 complex with an Fc␣ dimer by binding to each C H 2-C H 3 domain interface (20 -25).…”