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Transcriptional Regulation of NK Cell Receptors

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Immunobiology of Natural Killer Cell Receptors

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 298))

Abstract

The stochastic expression of individual members of NK cell receptor gene families on subsets ofNKcells has attracted considerable interest in the transcriptional regulation of these genes. Each receptor gene can contain up to three separate promoters with distinct properties. The recent discovery that an upstream promoter can function as a probabilistic switch element in the Ly49 gene family has revealed a novel mechanism of variegated gene expression. An important question to be answered is whether or not the other NK cell receptor gene families contain probabilistic switches. The promoter elements currently identified in the Ly49, NKR-P1, CD94, NKG2A, and KIR gene families are described.

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References

  • Brostjan C, Sobanov Y, Glienke J, Hayer S, Lehrach H, Francis F, Hofer E (2000) The NKG2 natural killer cell receptor family: comparative analysis of promoter sequences. Genes Immun 1:504–508

    Article  CAS  PubMed  Google Scholar 

  • Bull C, Sobanov Y, Rohrdanz B, O’Brien J, Lehrach H, Hofer E (2000) The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region. Genes Immun 1:280–287

    Article  CAS  PubMed  Google Scholar 

  • Carlyle JR, Martin A, Mehra A, Attisano L, Tsui FW, Zúñiga-Pflücker JC (1999) Mouse NKR-P1B, a novel NK1.1 antigen with inhibitory function. J Immunol 162:5917–5923

    CAS  PubMed  Google Scholar 

  • Carlyle JR, Michie AM, Furlonger C, Nakano T, Lenardo MJ, Paige CJ, Zúñiga-Pflücker JC (1997) Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes. J Exp Med 186:173–182

    Article  CAS  PubMed  Google Scholar 

  • Chan HW, Kurago ZB, Stewart CA, Wilson MJ, Martin MP, Mace BE, Carrington M, Trowsdale J, Lutz CT (2003) DNA methylation maintains allele-specific KIR gene expression in human natural killer cells. J Exp Med 197: 245–255

    Article  PubMed  Google Scholar 

  • Chuang SS, Pham HT, Kumaresan PR, Mathew PA (2001) A prominent role for activator protein-1 in the transcription of the human 2B4 (CD244) gene in NK cells. J Immunol 166:6188–6195

    CAS  PubMed  Google Scholar 

  • Dorfman JR, Raulet DH (1998) Acquisition of Ly49 receptor expression by developing natural killer cells. J Exp Med 187:609–618

    Article  CAS  PubMed  Google Scholar 

  • Gosselin P, Makrigiannis AP, Nalewaik R, Anderson SK (2000) Characterization of the Ly49I promoter. Immunogenetics 51:326–331

    Article  CAS  PubMed  Google Scholar 

  • Held W, Kunz B, Lowin-Kropf B, van de Wetering M, Clevers H (1999) Clonal acquisition of the Ly49A NK cell receptor is dependent on the trans-acting factor TCF-1. Immunity 11:433–442

    Article  CAS  PubMed  Google Scholar 

  • Held W, Clevers H, Grosschedl R (2003) Redundant functions of TCF-1 and LEF-1 during T and NK cell development, but unique role of TCF-1 for Ly49 NK cell receptor acquisition. Eur J Immunol 33:1393–1398

    Article  CAS  PubMed  Google Scholar 

  • Heusohn F, Wirries G, Schmidt RE, Gessner JE (2002) The Pmed1 gene promoter of human FcγRIIIA can function as a NK/T cell-specific restriction element, which involves binding of Sp1 transcription factor. J Immunol 168: 2857–2864

    CAS  PubMed  Google Scholar 

  • Ioannidis V, Kunz B, Tanamachi DM, Scarpellino L, Held W (2003) Initiation and limitation of Ly-49A NK cell receptor acquisition by T cell factor-1. J Immunol 171:769–775

    CAS  PubMed  Google Scholar 

  • Kravitz RH, Grendell RL, Slukvin II, Golos TG (2001) Selective expression of NKG2-A and NKG2-C m RNAs and novel alternative splicing of 5′ exons in rhesus monkey decidua. Immunogenetics 53:69–73

    Article  CAS  PubMed  Google Scholar 

  • Kubo S, Itoh Y, Ishikawa N, Nagasawa R, Mitarai T, Maruyama N (1993) The gene encoding mouse lymphocyte antigenLy-49: structural analysis and the 5′-flanking sequence. Gene 136:329–331

    Article  CAS  PubMed  Google Scholar 

  • Kubo S, Nagasawa R, Nishimura H, Shigemoto K, Maruyama N (1999) ATF-2-binding regulatory element is responsible for the Ly49A expression inmurine T lymphoid line, EL-4. Biochim Biophys Acta 1444:191–200

    CAS  PubMed  Google Scholar 

  • Kubota A, Kubota S, Lohwasser S, Mager DL, Takei F (1999) Diversity of NK cell receptor repertoire in adult and neonatal mice. J Immunol 163:212–216

    CAS  PubMed  Google Scholar 

  • Kung SKP, Su R-C, Shannon J, Miller RG (1999) The NKR-P1B gene product is an inhibitory receptor on SJL/J NK cells. J Immunol 162:5876–5887

    CAS  PubMed  Google Scholar 

  • Kunz B, Held W (2001) Positive and negative roles of the trans-acting T cell factor-1 for the acquisition of distinct Ly-49 MHC class I receptors by NK cells. J Immunol 166:6181–6187

    CAS  PubMed  Google Scholar 

  • Lacorazza HD, Miyazaki Y, Di Cristofano A, Deblasio A, Hedvat C, Zhang J, Cordon-Cardo C, Mao S, Pandolfi PP, and Nimer SD (2002) The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells. Immunity 17:437–439

    Article  CAS  PubMed  Google Scholar 

  • Lieto LD, Borrego F, You CH, Coligan JE (2003) Human CD94 gene expression: dual promoters differing in responsiveness to IL-2 or IL-15. J Immunol 171:5277–5286

    CAS  PubMed  Google Scholar 

  • Liu J, Morris MA, Nguyen P, George TC, Koulich E, Lai WC, Schatzle JD, Kumar V, Bennett M (2000) Ly49I NK cell receptor transgene inhibition of rejection of H2b mouse bone marrow transplants. J Immunol 164:1793–1799

    CAS  PubMed  Google Scholar 

  • Ljutic B, Carlyle JR, Zuniga-Pflucker JC (2003) Identification of upstream cis-acting regulatory elements controlling lineage-specific expression of the mouse NK cell activation receptor, NKR-P1C. J Biol Chem 278: 31909–31917

    Article  CAS  PubMed  Google Scholar 

  • Lohwasser S, Wilhelm B, Mager DL, Takei F (2000) The genomic organization of the mouse CD94 C-type lectin gene. Eur J Immunogenet 27:149–151

    Article  CAS  PubMed  Google Scholar 

  • McMahon CW, Raulet DH (2001) Expression and function of NK receptors in CD8+ T cells. Curr Opin Immunol 13:465–470

    Article  CAS  PubMed  Google Scholar 

  • McQueen KL, Wilhelm BT, Takei F, Mager DL (2001) Functional analysis of 5′ and 3′ regions of the closely related Ly49c and j genes. Immunogenetics 52:212–223

    Article  CAS  PubMed  Google Scholar 

  • Nguyen QT, Doyen N, d’Andon MF, Rougeon F (1991). Demonstration of a divergent transcript from the bidirectional heavy chain immunoglobulin promoter Vh441 in B-cells. Nucleic Acids Res 19:5339–5344

    CAS  PubMed  Google Scholar 

  • Plougastel B, Trowsdale J (1998) Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes. Genomics 49:193–199

    Article  CAS  PubMed  Google Scholar 

  • Raulet DH, Held W, Correa I, Dorfman J, Wu M-F, Corral L (1997) Specificity, tolerance and developmental regulation of natural killer cells defined by expression of class I specific Ly49 receptors. Immunol Rev 155: 41–52

    Article  CAS  PubMed  Google Scholar 

  • Roth C, Carlyle JR, Takizawa H, Raulet DH (2000) Clonal acquisition of inhibitory Ly49 receptors on developing NK cells is successively restricted and regulated by stromal class I MHC. Immunity 13:143–153

    Article  CAS  PubMed  Google Scholar 

  • Ryan JC, Turck J, Niemi EC, Yokoyama WM, Seaman WE (1992) Molecular cloning of the NK1.1 antigen, amember of the NKR-P1 family of natural killer cell activation molecules. J Immunol 149:1631–1635

    CAS  PubMed  Google Scholar 

  • Saleh A, Makrigiannis AP, Hodge DL, Anderson SK (2002) Identification of a novel Ly49 promoter that is active in bone marrow and fetal thymus. J Immunol 168:5163–5169

    CAS  PubMed  Google Scholar 

  • Saleh A, Davies GE, Pascal V, Wright PW, Hodge DL, Cho EH, Lockett SJ, Abshari M, Anderson SK (2004) Identification of probabilistic transcriptional switches in the Ly49 gene cluster: a eukaryotic mechanism for selective gene activation. Immunity 21:55–66

    Article  CAS  PubMed  Google Scholar 

  • Santourlidis S, Trompeter HI, Weinhold S, Eisermann B, Meyer KL, Wernet P, Uhrberg M (2002) Crucial role of DNA methylation in determination of clonally distributed killer cell Ig-like receptor expression patterns in NK cells. J Immunol 169:4253–4261

    CAS  PubMed  Google Scholar 

  • Schilham MW, Wilson A, Moerer P, Benaissa-Trouw BJ, Cumano A, Clevers HC (1998) Critical involvement of Tcf-1 in expansion of thymocytes. J Immunol 161:3984–3991

    CAS  PubMed  Google Scholar 

  • Stevenaert F, Van Beneden K, De Creus A, Debacker V, Plum J, Leclercq G (2003) Ly49E expression points toward overlapping, but distinct, natural killer (NK) cell differentiation kinetics and potential of fetal versus adult lymphoid progenitors. J Leukoc Biol 73:731–738

    Article  CAS  PubMed  Google Scholar 

  • Stewart CA, Van Bergen J, Trowsdale J (2003) Different and divergent regulation of the KIR2DL4 and KIR3DL1 promoters. J Immunol 170:6073–6081

    CAS  PubMed  Google Scholar 

  • Sun G, Kitchingman GR (1994) Bidirectional transcription from the human immunoglobulin VH6 gene promoter. Nucleic Acids Res 22:861–868

    CAS  PubMed  Google Scholar 

  • Takei F, McQueen KL, Maeda M, Wilhelm BT, Lohwasser S, Lian RH, Mager DL (2001) Ly49 and CD94/NKG2: developmentally regulated expression and evolution. Immunol Rev 181:90–103

    Article  CAS  PubMed  Google Scholar 

  • Tanamachi DM, Moniot DC, Cado D, Liu SD, Hsia JK, Raulet DH (2004) Genomic Ly49A transgenes: basis of variegated Ly49A gene expression and identification of a critical regulatory element. J Immunol 172:1074–1082

    CAS  PubMed  Google Scholar 

  • Trowsdale J, Barten R, Haude A, Stewart CA, Beck S, Wilson MJ (2001) The genomic context of natural killer receptor extended gene families. Immunol Rev 181:20–38

    Article  CAS  PubMed  Google Scholar 

  • Tsutsui H, Nakanishi K, Matsui K, Higashino K, Okamura H, Miyazawa Y, Kaneda K. (1996). IFN-γ-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. J Immunol 157: 3967–3973

    CAS  PubMed  Google Scholar 

  • Valiante NM, Uhrberg M, Shilling HG, Lienert-Weidenbach K, Arnett KL, D’Andrea A, Phillips JH, Lanier LL, Parham P (1997) Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity 7:739–751

    Article  CAS  PubMed  Google Scholar 

  • Vilches C, Gardiner CM, Parham P (2000) Gene structure and promoter variation of expressed and nonexpressed variants of the KIR2DL5 gene. J Immunol 165:6416–6421

    CAS  PubMed  Google Scholar 

  • Wang J-W, Howson JM, Ghansah T, Desponts C, Ninos JM, May SL, Nguyen KHT, Toyama-Sorimachi N, Kerr WG (2002) Influence of SHIP on the NK repertoire and allogeneic bone marrow transplantation. Science 295:2094–2097

    Article  CAS  PubMed  Google Scholar 

  • Wilhelm BT, McQueen KL, Freeman JD, Takei F, Mager DL (2001) Comparative analysis of the promoter regions and transcriptional start sites of mouse Ly49 genes. Immunogenetics 53:215–224

    Article  CAS  PubMed  Google Scholar 

  • Wilhelm BT, Landry JR, Takei F, Mager DL (2003) Transcriptional control of murine CD94 gene: differential usage of dual promoters by lymphoid cell types. J Immunol 171:4219–4226

    CAS  PubMed  Google Scholar 

  • Williams NS, Kubota A, Bennett M, Kumar V, Takei F (2000). Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression. Eur J Immunol 30:2074–2082

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Basic Research Program, SAIC-Frederick, Bldg. 560, Rm. 31-93, Frederick, MD, 21702-1201, USA

    S. K. Anderson

Authors
  1. S. K. Anderson
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Correspondence to S. K. Anderson .

Editor information

Editors and Affiliations

  1. Atlanta, Georgia

    R.W. Compans

  2. Birmingham, Alabama

    M.D. Cooper

  3. Kyoto

    T. Honjo

  4. Philadelphia, Pennsylvania

    H. Koprowski

  5. Basel

    F. Melchers

  6. La Jolla, California

    M.B.A. Oldstone

  7. Oslo

    S. Olsnes

  8. Bethesda, Maryland

    M. Potter

  9. La Jolla, California

    P.K. Vogt

  10. Munich

    H. Wagner

  11. Laboratory of NK Cells and Innate Immunity, Centre d’Immunologie de Marseille-Luminy (CIML), CNRS-INSERM-Université de la Méditerranée, Campus de Luminy, Case 906, 13288, Marseille Cedex 09, France

    Eric Vivier DVM, PhD.

  12. Department of Pathology and Immunology, Washington University School of Medicine, West Building, Rooms 4724, Box 8118 660 South Euclid Ave, St. Louis, MO, 63110, USA

    Marco Colonna M.D.

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© 2006 Springer-Verlag Berlin Heidelberg

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Anderson, S.K. (2006). Transcriptional Regulation of NK Cell Receptors. In: Compans, R., et al. Immunobiology of Natural Killer Cell Receptors. Current Topics in Microbiology and Immunology, vol 298. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27743-9_3

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