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Human KIR2DL5 Is an Inhibitory Receptor Expressed on the Surface of NK and T Lymphocyte Subsets¹

Ernesto Estefanía^*, Raquel Flores, Natalia Gómez-Lozano^*, Helena Aguilar, Miguel López-Botet and Carlos Vilches^2,*

^* Servicio de Inmunología, Hospital Universitario Puerta de Hierro, Madrid, Spain; and Molecular Immunopathology Unit, Universitat Pompeu Fabra (DCEXS), Barcelona, Spain

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 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants FIS01/0381, BMC2001-0265, and BFU2005-04622 (to C.V.), and SAF2001-0696 (to M.L.-B.). E.E. and N.G.L. were supported sequentially by fellowships from Fundación Leukocyte Antigen and Immune Response and Instituto de Salud Carlos III (CM0500026 and CM0300028, respectively).

² Address correspondence and reprint requests to Dr. Carlos Vilches, Inmunología, Hospital Universitario Puerta de Hierro, San Martín de Porres 4, 28035 Madrid, Spain. E-mail address: carlos.vilches{at}yahoo.com

³ Abbreviations used in this paper: KIR, killer cell Ig-like receptor; HA, hemagglutinin; D0, D1, D2, Ig-like domains 0, 1, and 2; SHP-1 and SHP-2, Src homology region 2-containing protein tyrosine phosphatases-1 and -2; HEK, human embryonic kidney; PNGaseF, peptide N-glycosidase F.

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