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PROW: KIR
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PROW presents the FAMILY:
KIR
Authors: Eric O. Long, Marco Colonna, Lewis L. Lanier
Reviewer: Miguel Lopez-Botet


 ABSTRACT FOR KIR FAMILY

Killer cell immunoglobulin (Ig)-like receptors (KIR), also called killer cell inhibitory receptors, are glycoproteins expressed in natural killer (NK) cells and some T cells. The KIR family is estimated to include about 11 genes. Some members of the KIR family bind specifically to certain HLA class I allotypes. Ligation of such KIR by HLA class I molecules on target cells results in inhibition of the NK or T cell cytotoxic activity. The KIR family is subdivided into two subfamilies based on structure. Some KIR members have two Ig domains (KIR2D), others have three Ig domains (KIR3D). KIR members vary also in the length of the cytoplasmic tails. Typically, KIR with a long cytoplasmic tail (L) deliver an inhibitory signal, whereas KIR with a short cytoplasmic tail (S) can activate NK or T cell responses


 MEMBERS & NOMENCLATURE OF THE KIR FAMILY
  • KIR2DL subfamily
  • KIR2DS subfamily
  • KIR3DL subfamily
  • KIR3DS subfamily

  •  AMINO ACID SEQUENCE ALIGNMENT OF KIR

     MAJOR LINKS FOR KIR
     BIOCHEMICAL ACTIVITY OF KIR
     ASSOCIATED MOLECULES OF KIR
     
    SHP-1  The long cytoplasmic tails bind the tyrosine phosphatase SHP-1 through two tyrosine-phosphorylated ITIM sequences [I/V]xYxxL (Burshtyn et al. 1996; Olcese et al. 1996; Campbell et al. 1996; Fry et al. 1996; Burshtyn et al. 1997)
    DAP12 KIR isoforms with short cytoplasmic tails associate with a disulfide linked dimer of 14 kDa phosphoproteins called DAP12. DAP12 is also known as KARAP (Killer activating receptor associated protein)*(Olcese et al. 1997; Lanier et al. 1998)


     CELLULAR FUNCTION OF KIR
     EXPRESSION OF KIR
     DISEASE RELEVANCE AND FUNCTION OF KIR IN INTACT ANIMAL
     STRUCTURE OF  KIR
     GENOMICS OF KIR
     AUTHORS' INSIGHTS FOR KIR
  • cDNA Information

  •  
    REFERENCES FOR KIR

    REVIEWS

    Lanier LL. NK cell receptors. Annu. Rev. Immunol. 1998 16:359 PubMed

    Moretta A, Bottino C, Vitale M, Pende D, Biassoni R, Mingari MC and Moretta L. Receptors for HLA class-I molecules in human natural killer cells. Annu. Rev. Immunol. 1996 14:619 PubMed

    Parham, P.(Ed) (1997). NK cells, MHC class I antigens and missing self. Immunol. Rev. 155, 5-221

    PRIMARY CITATIONS

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    Biassoni R, Cantoni C, Falco M, Verdiani S, Bottino C, Vitale M, Conte R, Poggi A, Moretta A and Moretta L. The human leukocyte antigen (HLA)-C-specific 'activatory' or 'inhibitory' natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions. J. Exp. Med. 1996 183:645 PubMed

    Biassoni R, Pessino A, Malaspina A, Cantoni C, Bottino C, Sivori S, Moretta L and Moretta A. Role of amino acid position 70 in the binding affinity of p50.1 and p58.1 receptors for HLA-Cw4 molecules. Eur. J. Immunol. 1997 27:3095 PubMed

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    Braud VM, Allan DS, O'Callaghan CA, Soderstrom K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL and McMichael AJ. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1998 391:795 PubMed

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    Cosman D, Fanger N, Borges L, Kubin M, Chin W, Peterson L and Hsu ML. A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity 1997 7:273 PubMed

    D'Andrea A, Chang C, Franz-Bacon K, McClanahan T, Phillips JH and Lanier LL. Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes. J. Immunol. 1995 155:2306 PubMed

    D'Andrea A, Chang C, Phillips JH and Lanier LL. Regulation of T cell lymphokine production by killer cell inhibitory receptor recognition of self HLA class I alleles. J. Exp. Med. 1996 184:789 PubMed

    Dohring C, Samaridis J and Colonna M. Alternatively spliced forms of human killer inhibitory receptors. Immunogenetics 1996a 44:227 PubMed

    Dohring C, Scheidegger D, Samaridis J, Cella M and Colonna M. A human killer inhibitory receptor specific for HLA-A1,2. J. Immunol. 1996b 156:3098 PubMed

    Fan QR, Mosyak L, Winter CC, Wagtmann N, Long EO and Wiley DC. Structure of the inhibitory receptor for human natural killer cells resembles haematopoietic receptors. Nature 1997 389:96 PubMed

    Ferrini S, Cambiaggi A, Meazza R, Sforzini S, Marciano S, Mingari MC and Moretta L. T cell clones expressing the natural killer cell-related p58 receptor molecule display heterogeneity in phenotypic properties and p58 function. Eur. J. Immunol. 1994 24:2294 PubMed

    Fry AM, Lanier LL and Weiss A. Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C. J. Exp. Med. 1996 184:295 PubMed

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    Hayami K, Fukuta D, Nishikawa Y, Yamashita Y, Inui M, Ohyama Y, Hikida M, Ohmori H and Takai T. Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors. J. Biol. Chem. 1997 272:7320 PubMed

    Ikeda H, Lethe B, Lehmann F, van Baren N, Baurain JF, de Smet C, Chambost H, Vitale M, Moretta A, Boon T and Coulie PG. Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity 1997 6:199 PubMed

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    Lazetic S, Chang C, Houchins JP, Lanier LL and Phillips JH. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J. Immunol. 1996 157:4741 PubMed

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    Moretta A, Bottino C, Pende D, Tripodi G, Tambussi G, Viale O, Orengo A, Barbaresi M, Merli A, Ciccone E, et al. Identification of four subsets of human CD3-CD16+ natural killer (NK) cells by the expression of clonally distributed functional surface molecules: correlation between subset assignment of NK clones and ability to mediate specific alloantigen recognition. J. Exp. Med. 1990a 172:1589 PubMed**

    Moretta A, Sivori S, Vitale M, Pende D, Morelli L, Augugliaro R, Bottino C and Moretta L. Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells. J. Exp. Med. 1995 182:875 PubMed

    Moretta A, Tambussi G, Bottino C, Tripodi G, Merli A, Ciccone E, Pantaleo G and Moretta L. A novel surface antigen expressed by a subset of human CD3- CD16+ natural killer cells. Role in cell activation and regulation of cytolytic function. J. Exp. Med. 1990b 171:695 PubMed

    Moretta A, Vitale M, Bottino C, Orengo AM, Morelli L, Augugliaro R, Barbaresi M, Ciccone E and Moretta L. P58 molecules as putative receptors for major histocompatibility complex (MHC) class I molecules in human natural killer (NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells in NK clones displaying different specificities. J. Exp. Med. 1993 178:597 PubMed

    Olcese L, Cambiaggi A, Semenzato G, Bottino C, Moretta A and Vivier E. Human killer cell activatory receptors for MHC class I molecules are included in a multimeric complex expressed by natural killer cells. J. Immunol. 1997 158:5083 PubMed

    Olcese L, Lang P, Vely F, Cambiaggi A, Marguet D, Blery M, Hippen KL, Biassoni R, Moretta A, Moretta L, Cambier JC and Vivier E. Human and mouse killer-cell inhibitory receptors recruit PTP1C and PTP1D protein tyrosine phosphatases. J. Immunol. 1996 156:4531 PubMed

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    * indicates ammended by reviewer, ** indicates added by reviewer

    Modified 10/15/99   mpr@mail.nih.gov