Gene Symbol: Klra4
Description: killer cell lectin-like receptor, subfamily A, member 4
Alias: Chok, Klra32, Klra33, Ly-49d, Ly49d, ly49r<129>, killer cell lectin-like receptor 4, T-cell surface glycoprotein Ly-49D, killer cell lectin-like receptor subfamily A member 32, killer cell lectin-like receptor subfamily A member 33, lymphocyte antigen 49d
Species: mouse
Products:     Klra4

Top Publications

  1. Yokoyama W, Kehn P, Cohen D, Shevach E. Chromosomal location of the Ly-49 (A1, YE1/48) multigene family. Genetic association with the NK 1.1 antigen. J Immunol. 1990;145:2353-8 pubmed
    ..1 and Ly-49, approximately 10% of CD3+ cells coexpressed Ly-49. The chromosomal mapping data and the expression of the Ly-49 and NK1.1 Ag suggest that the NK1.1 Ag may be a member of the Ly-49 multigene family. ..
  2. Brown M, Fulmek S, Matsumoto K, Cho R, Lyons P, Levy E, et al. A 2-Mb YAC contig and physical map of the natural killer gene complex on mouse chromosome 6. Genomics. 1997;42:16-25 pubmed
    ..The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens. ..
  3. Vance R, Tanamachi D, Hanke T, Raulet D. Cloning of a mouse homolog of CD94 extends the family of C-type lectins on murine natural killer cells. Eur J Immunol. 1997;27:3236-41 pubmed
    ..Murine homologs of human NKG2 family members have not yet been identified, but we report here the existence of a murine NKG2D-like sequence that also maps to the murine NK complex near CD94 and Ly49 family members. ..
  4. Ho E, Heusel J, Brown M, Matsumoto K, Scalzo A, Yokoyama W. Murine Nkg2d and Cd94 are clustered within the natural killer complex and are expressed independently in natural killer cells. Proc Natl Acad Sci U S A. 1998;95:6320-5 pubmed
    ..Thus, these data indicate the expanding complexity of the NK complex and the corresponding repertoire of C-type lectin-like receptors on murine NK cells. ..
  5. Yokoyama W. Hybrid resistance and the Ly-49 family of natural killer cell receptors. J Exp Med. 1995;182:273-7 pubmed
  6. Nabekura T, Lanier L. Activating Receptors for Self-MHC Class I Enhance Effector Functions and Memory Differentiation of NK Cells during Mouse Cytomegalovirus Infection. Immunity. 2016;45:74-82 pubmed publisher
    ..Here, we address how the activating Ly49D receptor impacts the NK cell response to mouse cytomegalovirus (MCMV) infection by comparing the activation and ..
  7. Liu J, Liu S, Xia M, Xu S, Wang C, Bao Y, et al. Rhomboid domain-containing protein 3 is a negative regulator of TLR3-triggered natural killer cell activation. Proc Natl Acad Sci U S A. 2013;110:7814-9 pubmed publisher
    ..Our study outlines a mechanism for the negative regulation of NK cell activation and also provides clues for the function of the rhomboid proteins in immunity. ..
  8. Tassi I, Le Friec G, Gilfillan S, Takai T, Yokoyama W, Colonna M. DAP10 associates with Ly49 receptors but contributes minimally to their expression and function in vivo. Eur J Immunol. 2009;39:1129-35 pubmed publisher
    ..Although initial studies indicated that Ly49H and Ly49D recruit only DAP12, a recent report suggested that they also associate with DAP10...
  9. Townsend M, Weinmann A, Matsuda J, Salomon R, Farnham P, Biron C, et al. T-bet regulates the terminal maturation and homeostasis of NK and Valpha14i NKT cells. Immunity. 2004;20:477-94 pubmed
    ..Our results identify T-bet as a key factor in the terminal maturation and peripheral homeostasis of NK and Valpha14i NKT cells. ..

More Information


  1. Koike J, Wakao H, Ishizuka Y, Sato T, Hamaoki M, Seino K, et al. Bone marrow allograft rejection mediated by a novel murine NK receptor, NKG2I. J Exp Med. 2004;199:137-44 pubmed
    ..NKG2I is a novel activating receptor mediating recognition and rejection of allogeneic target cells. ..
  2. Kawamura T, Koka R, Ma A, Kumar V. Differential roles for IL-15R alpha-chain in NK cell development and Ly-49 induction. J Immunol. 2003;171:5085-90 pubmed
    ..These results indicate a novel role for IL-15Ralpha-chain in Ly-49 induction on developing NK cells...
  3. Mason L, Willette Brown J, Anderson S, Alvord W, Klabansky R, Young H, et al. Receptor glycosylation regulates Ly-49 binding to MHC class I. J Immunol. 2003;171:4235-42 pubmed
    ..Therefore, the addition of complex carbohydrates to the Ly-49 family of receptors may represent a mechanism by which NK cells regulate affinity for host class I ligands. ..
  4. Lowin Kropf B, Kunz B, Schneider P, Held W. A role for the src family kinase Fyn in NK cell activation and the formation of the repertoire of Ly49 receptors. Eur J Immunol. 2002;32:773-82 pubmed
    ..NK cells may acquire Ly49 receptors until they generate sufficient inhibitory signals to balance their activation levels. Such a process would ensure the induction of NK cell self-tolerance. ..
  5. Makrigiannis A, Pau A, Schwartzberg P, McVicar D, Beck T, Anderson S. A BAC contig map of the Ly49 gene cluster in 129 mice reveals extensive differences in gene content relative to C57BL/6 mice. Genomics. 2002;79:437-44 pubmed
    ..These results indicate that Ly49 gene numbers can be significantly different between inbred mouse strains, analogous to the haplotype differences observed in the human KIR genes. ..
  6. Kunz B, Held W. 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. 2001;166:6181-7 pubmed
    ..These findings reveal an important role of TCF-1 for the formation of the NK cell receptor repertoire. ..
  7. Silver E, Gong D, Chang C, Amrani A, Santamaria P, Kane K. Ly-49P activates NK-mediated lysis by recognizing H-2Dd. J Immunol. 2000;165:1771-81 pubmed
    ..Thus, Ly-49P is the second activating Ly-49 receptor demonstrated to induce NK cytotoxicity by recognizing a class I MHC molecule. ..
  8. Idris A, Scalzo A, Yokoyama W. Close genetic linkage of Chok with the NKC-linked loci Cd94, Ly49, and Cmv1 on mouse chromosome 6. Immunogenetics. 1999;49:906-8 pubmed
  9. Idris A, Iizuka K, Smith H, Scalzo A, Yokoyama W. Genetic control of natural killing and in vivo tumor elimination by the Chok locus. J Exp Med. 1998;188:2243-56 pubmed
    ..Genetic mapping studies revealed linkage between the locus influencing CHO killing, termed Chok, and loci encoded within the NK gene complex (NKC), suggesting that Chok encodes an NK cell receptor specific for ..
  10. Silver E, Elliott J, Kane K. Alternatively spliced Ly-49D and H transcripts are found in IL-2-activated NK cells. Immunogenetics. 1996;44:478-82 pubmed
  11. Smith H, Karlhofer F, Yokoyama W. Ly-49 multigene family expressed by IL-2-activated NK cells. J Immunol. 1994;153:1068-79 pubmed
    ..Thus, IL-2-activated NK cells express mRNAs for multiple, Ly-49-related molecules. ..
  12. Makrigiannis A, Pau A, Saleh A, Winkler Pickett R, Ortaldo J, Anderson S. Class I MHC-binding characteristics of the 129/J Ly49 repertoire. J Immunol. 2001;166:5034-43 pubmed
    ..Ly49 divergence should be considered when using 129-derived embryonic stem cells for the production of gene-targeted mice, especially when an immune or NK-derived phenotype is under scrutiny. ..
  13. Wilhelm B, McQueen K, Freeman J, Takei F, Mager D. Comparative analysis of the promoter regions and transcriptional start sites of mouse Ly49 genes. Immunogenetics. 2001;53:215-24 pubmed
    ..Our data suggest that differences in the location of transcriptional start sites contribute to the observed complexity in receptor repertoire patterns. ..
  14. Brown M, Zhang J, Du Y, Stoll J, Yokoyama W, Scalzo A. Localization on a physical map of the NKC-linked Cmv1 locus between Ly49b and the Prp gene cluster on mouse chromosome 6. J Immunol. 1999;163:1991-9 pubmed
    ..This high resolution, integrated physical and genetic NKC map will facilitate identification of Cmv1 and other NKC-linked loci that regulate NK cell-mediated immunity. ..
  15. Furukawa H, Iizuka K, Poursine Laurent J, Shastri N, Yokoyama W. A ligand for the murine NK activation receptor Ly-49D: activation of tolerized NK cells from beta 2-microglobulin-deficient mice. J Immunol. 2002;169:126-36 pubmed
  16. Ortaldo J, Young H. Expression of IFN-gamma upon triggering of activating Ly49D NK receptors in vitro and in vivo: costimulation with IL-12 or IL-18 overrides inhibitory receptors. J Immunol. 2003;170:1763-9 pubmed
    ..In this report we demonstrate that costimulation of the activating Ly49D murine NK cell receptor with IL-12 or IL-18 is capable of over-riding the inhibitory Ly49G2 receptor blockade for ..
  17. Voyle R, Beermann F, Lees R, Schumann J, Zimmer J, Held W, et al. Ligand-dependent inhibition of CD1d-restricted NKT cell development in mice transgenic for the activating receptor Ly49D. J Exp Med. 2003;197:919-25 pubmed
    ..We have produced mice transgenic for the ITAM-associated Ly49D and ITIM-containing Ly49A receptors and their common ligand H2-Dd to determine the importance of these signaling ..
  18. Hart G, Flaishon L, Becker Herman S, Shachar I. Ly49D receptor expressed on immature B cells regulates their IFN-gamma secretion, actin polymerization, and homing. J Immunol. 2003;171:4630-8 pubmed
    ..We show that the MHC class I receptor, Ly49D, is expressed on immature B cells and is down-regulated during maturation...
  19. Idris A, Smith H, Mason L, Ortaldo J, Scalzo A, Yokoyama W. The natural killer gene complex genetic locus Chok encodes Ly-49D, a target recognition receptor that activates natural killing. Proc Natl Acad Sci U S A. 1999;96:6330-5 pubmed
    ..The localization of Chok in the NK gene complex suggested that it may encode either an activating or an inhibitory receptor...
  20. Merck E, Voyle R, MacDonald H. Ly49D engagement on T lymphocytes induces TCR-independent activation and CD8 effector functions that control tumor growth. J Immunol. 2009;182:183-92 pubmed
    ..Transgenic mice expressing the activating receptor Ly49D/DAP12 offer the opportunity to better understand the relevance of ITAM signaling in the biology of T cells...
  21. Lanier L, Phillips J. Inhibitory MHC class I receptors on NK cells and T cells. Immunol Today. 1996;17:86-91 pubmed
    ..Genes encoding the murine and human NK-cell receptors have been cloned, and studies of their structure, function and expression are progressing rapidly, as reviewed here by Lewis Lanier and Joseph Phillips. ..
  22. Wong S, Freeman J, Kelleher C, Mager D, Takei F. Ly-49 multigene family. New members of a superfamily of type II membrane proteins with lectin-like domains. J Immunol. 1991;147:1417-23 pubmed
    ..These results demonstrate the existence of several functional genes that are highly related to Ly-49. These genes comprise a subfamily within the superfamily of type II transmembrane proteins containing CRD. ..