Human KIR2DL5 is an inhibitory receptor expressed on the surface of NK and T lymphocyte subsets.
Human NK cells, by means of a repertoire of clonally distributed killer cell Ig-like receptors (KIR), survey the expression of individual self HLA class I molecules, which is often altered in infections and tumors. KIR2DL5 (CD158f) is the last identified KIR gene and, with KIR2DL4, constitutes a structurally divergent lineage conserved in different primate species. Research on KIR2DL5 has thus far been limited to its genetic aspects due to a lack of reagents to detect its product. We report here the identification and characterization of the receptor encoded by KIR2DL5 using a newly generated specific mAb that recognizes its most commonly expressed allele, KIR2DL5A*001. KIR2DL5 displays a variegated distribution on the surface of CD56(dim) NK cells. This contrasts with the expression pattern of its structural homolog KIR2DL4 (ubiquitous transcription, surface expression restricted to CD56(bright) NK cells) and resembles the profile of KIR recognizing classical HLA class I molecules. Like other MHC class I receptors, KIR2DL5 is also found in a variable proportion of T lymphocytes. KIR2DL5 is detected on the cell surface as a monomer of approximately 60 kDa that, upon tyrosine phosphorylation, recruits the Src homology region 2-containing protein tyrosine phosphatase-2 and, to a lesser extent, Src homology region 2-containing protein tyrosine phosphatase-1. Ab-mediated cross-linking of KIR2DL5 inhibits NK cell cytotoxicity against murine FcR+ P815 cells. KIR2DL5 is thus an inhibitory receptor gathering a combination of genetic, structural, and functional features unique among KIR, which suggests that KIR2DL5 plays a specialized role in innate immunity.
Estefanía
Ernesto
E
Servicio de Inmunología, Hospital Universitario Puerta de Hierro, San Martín de Porres 4, 28035 Madrid, Spain.
Flores
Raquel
R
Gómez-Lozano
Natalia
N
Aguilar
Helena
H
López-Botet
Miguel
M
Vilches
Carlos
C
D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D019002:CD56 Antigen / Q000032:analysis; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D054346:Receptors, KIR2DL5; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D019002:CD56 Antigen; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C515079:KIR2DL4 protein, human; C515080:KIR2DL5A protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054345:Receptors, KIR2DL4; D054346:Receptors, KIR2DL5; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse