Gene Symbol: Klra1
Description: killer cell lectin-like receptor, subfamily A, member 1
Alias: CH29-493D4.3, Klra22, Ly49a, Ly49o<129>, Ly49v, T-cell surface glycoprotein YE1/48, class I MHC receptor KLRA22, ly-49a, lymphocyte antigen 49a, natural killer cell receptor Ly49A, novel killer cell lectin-like receptor subfamily A protein, t lymphocyte antigen A1
Species: mouse
Products:     Klra1

Top Publications

  1. Yokoyama W, Ryan J, Hunter J, Smith H, Stark M, Seaman W. cDNA cloning of mouse NKR-P1 and genetic linkage with LY-49. Identification of a natural killer cell gene complex on mouse chromosome 6. J Immunol. 1991;147:3229-36 pubmed
    ..We have termed this genetic region the NK complex. ..
  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. Daniels B, Karlhofer F, Seaman W, Yokoyama W. A natural killer cell receptor specific for a major histocompatibility complex class I molecule. J Exp Med. 1994;180:687-92 pubmed
    ..Monoclonal antibody blocking experiments confirmed this interaction. These studies indicate that the specificity of natural killing is influenced by NK cell receptors that engage target cell MHC class I molecules. ..
  4. Stoneman E, Bennett M, An J, Chesnut K, Wakeland E, Scheerer J, et al. Cloning and characterization of 5E6(Ly-49C), a receptor molecule expressed on a subset of murine natural killer cells. J Exp Med. 1995;182:305-13 pubmed
    ..Thus, there appears to be allelic exclusion of 5E6 expression that may be related to the ability of F1 hybrid mice to reject parental H-2d bone marrow cell grafts. ..
  5. Saleh A, Makrigiannis A, Hodge D, Anderson S. Identification of a novel Ly49 promoter that is active in bone marrow and fetal thymus. J Immunol. 2002;168:5163-9 pubmed
    ..are present 4-10 kb upstream of Pro-2 in all Ly49 genes examined, and Pro-1 transcripts were detected from the Ly49a, e, g, o, and v genes...
  6. Yokoyama W, Jacobs L, Kanagawa O, Shevach E, Cohen D. A murine T lymphocyte antigen belongs to a supergene family of type II integral membrane proteins. J Immunol. 1989;143:1379-86 pubmed
  7. Scalzo A, Fitzgerald N, Wallace C, Gibbons A, Smart Y, Burton R, et al. The effect of the Cmv-1 resistance gene, which is linked to the natural killer cell gene complex, is mediated by natural killer cells. J Immunol. 1992;149:581-9 pubmed
    ..1 and other loci that reside on a distal segment of murine chromosome 6 in a region that has recently been defined as the natural killer complex. ..
  8. 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. ..
  9. 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. ..

More Information


  1. Held W, Roland J, Raulet D. Allelic exclusion of Ly49-family genes encoding class I MHC-specific receptors on NK cells. Nature. 1995;376:355-8 pubmed
    ..Accordingly, the Ly49A NK-cell antigen receptor has been shown to deliver an inhibitory signal to NK cells on encounter with Dd or Dk ..
  2. Karlhofer F, Orihuela M, Yokoyama W. Ly-49-independent natural killer (NK) cell specificity revealed by NK cell clones derived from p53-deficient mice. J Exp Med. 1995;181:1785-95 pubmed
  3. 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. ..
  4. 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. ..
  5. 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
  6. Orr M, Beilke J, Proekt I, Lanier L. Natural killer cells in NOD.NK1.1 mice acquire cytolytic function during viral infection and provide protection against cytomegalovirus. Proc Natl Acad Sci U S A. 2010;107:15844-9 pubmed publisher
    ..g7 NK cells, even in the absence of T cells and B cells. Thus, the impaired cytotoxic function of NK cells in NOD mice is alleviated by viral infection, which enables NOD NK cells to efficiently control MCMV infection. ..
  7. Held W, Raulet D. Expression of the Ly49A gene in murine natural killer cell clones is predominantly but not exclusively mono-allelic. Eur J Immunol. 1997;27:2876-84 pubmed
    ..earlier studies of polyclonal NK cell populations, we have employed an analysis of short-term NK cell clones from Ly49A heterozygous mice, to demonstrate that the Ly49A gene is usually expressed from one or the other allele in each ..
  8. 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. ..
  9. Kim S, Lalani S, Parekh V, Vincent T, Wu L, Van Kaer L. Impact of bacteria on the phenotype, functions, and therapeutic activities of invariant NKT cells in mice. J Clin Invest. 2008;118:2301-15 pubmed publisher
    ..These findings may have important implications for the development of iNKT cell-based therapies. ..
  10. Depatie C, Chalifour A, Pare C, Lee S, Vidal S, Lemieux S. Assessment of Cmv1 candidates by genetic mapping and in vivo antibody depletion of NK cell subsets. Int Immunol. 1999;11:1541-51 pubmed
    ..members for the resistance locus, first we followed the co-segregation of Cd94, Nkg2d, and the well-characterized Ly49a, Ly49c and Ly49g genes with respect to Cmv1 in pre-existing panels of intraspecific backcross mice...
  11. Tormo J, Natarajan K, Margulies D, Mariuzza R. Crystal structure of a lectin-like natural killer cell receptor bound to its MHC class I ligand. Nature. 1999;402:623-31 pubmed
    ..The murine NK receptor Ly49A inhibits NK cell activity by interacting with H-2D(d) through its C-type-lectin-like NK receptor domain...
  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
    ..b>Ly49V bound to many types of class I MHC, suggesting that Ly49V(+) NK cells may monitor host cells for a global down-..
  13. Mehta I, Wang J, Roland J, Margulies D, Yokoyama W. Ly49A allelic variation and MHC class I specificity. Immunogenetics. 2001;53:572-83 pubmed
    ..The best-characterized Ly49 molecule, the C57BL/6 form of Ly49A, is an NK cell inhibitory receptor that binds H2Dd...
  14. 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. ..
  15. Li Y, Guo K, Chen H, Li J, Wang F, Xie K, et al. [In vitro study of the killing activities on H-2(d) murine normal and tumor cells by Ly49A gene transfected lymphocytes]. Zhonghua Xue Ye Xue Za Zhi. 2001;22:235-7 pubmed
    To observe the killing activities of Ly49A gene transfected lymphocytes of C57BL/6 mice to normal and tumor cells of BALB/c mice. pLXSN-Ly49A retrovirus vector was constructed and packaged with PA317 cell line...
  16. Basiri H, Kiura K, DeNardin E, Nakamura I. Allospecificities of B6D2F1 hybrid NK cell subsets defined by Ly-49A expression. J Immunol. 1995;155:2822-32 pubmed
    ..The results, therefore, favor the view that the Hh-1 phenotype of the target cells may be defined largely by the effector cell's recognition of class I Ags on the target cell surface. ..
  17. Brown M, Scalzo A, Matsumoto K, Yokoyama W. The natural killer gene complex: a genetic basis for understanding natural killer cell function and innate immunity. Immunol Rev. 1997;155:53-65 pubmed
    ..Thus, further elucidation of the NKC and its gene products will provide a genetic basis for understanding innate immunity and NK-cell activity at the molecular level. ..
  18. Gays F, Koh A, Mickiewicz K, Aust J, Brooks C. Comprehensive analysis of transcript start sites in ly49 genes reveals an unexpected relationship with gene function and a lack of upstream promoters. PLoS ONE. 2011;6:e18475 pubmed publisher
    ..5'-RACE technique revealed that the genes encoding the "missing self" inhibitory receptors, Ly49A, C, G, and I, were transcribed from multiple broad regions in exon 1, in the intron1/exon2 region, and upstream of ..
  19. Chambers C, Kang J, Wu Y, Held W, Raulet D, Allison J. The lymphoproliferative defect in CTLA-4-deficient mice is ameliorated by an inhibitory NK cell receptor. Blood. 2002;99:4509-16 pubmed
    ..In this report we show that NK cell inhibitory receptor Ly49A engagement on T cells dramatically limits T-cell activation and the resultant lymphoproliferative disorder that ..
  20. Waldenström M, Achour A, Michaelsson J, Rolle A, Karre K. The role of an exposed loop in the alpha2 domain in the mouse MHC class I H-2Dd molecule for recognition by the monoclonal antibody 34-5-8S and the NK-cell receptor Ly49A. Scand J Immunol. 2002;55:129-39 pubmed
    ..mediating the protective effect of the MHC class I molecule H-2Dd (Dd), recognized by the inhibitory receptor Ly49A, has been mapped to the alpha1/alpha2 domains...
  21. Iizuka K, Naidenko O, Plougastel B, Fremont D, Yokoyama W. Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors. Nat Immunol. 2003;4:801-7 pubmed
  22. Barao I, Alvarez M, Ames E, Orr M, Stefanski H, Blazar B, et al. Mouse Ly49G2+ NK cells dominate early responses during both immune reconstitution and activation independently of MHC. Blood. 2011;117:7032-41 pubmed publisher
    ..These data suggest that the inhibitory Ly49G2 receptor represents an activation marker on mouse NK cells under various conditions. ..
  23. 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. ..
  24. Chalifour A, Scarpellino L, Back J, Brodin P, Devevre E, Gros F, et al. A Role for cis Interaction between the Inhibitory Ly49A receptor and MHC class I for natural killer cell education. Immunity. 2009;30:337-47 pubmed publisher
    ..However, the inhibitory Ly49A receptor can also bind MHC-I ligand on the NK cell itself (in cis)...
  25. Pauza M, Smith K, Neal H, Reilly C, Lanier L, Lo D. Transgenic expression of Ly-49A in thymocytes alters repertoire selection. J Immunol. 2000;164:884-92 pubmed
    ..Since Ly-49A may shift the signaling threshold of TCR-induced triggering, inducible expression of Ly-49A may regulate peripheral memory/activated T cells by raising the threshold for T cell reactivation. ..
  26. Zajac A, Vance R, Held W, Sourdive D, Altman J, Raulet D, et al. Impaired anti-viral T cell responses due to expression of the Ly49A inhibitory receptor. J Immunol. 1999;163:5526-34 pubmed
    ..we have studied anti-viral immune responses in mice transgenic for a class I-specific inhibitory receptor, Ly49A. Although nontransgenic mice express Ly49A primarily on NK cells and some T cells, the Ly49A transgenic mice ..
  27. Ito D, Iizuka Y, Katepalli M, Iizuka K. Essential role of the Ly49A stalk region for immunological synapse formation and signaling. Proc Natl Acad Sci U S A. 2009;106:11264-9 pubmed publisher
    ..Using a prototypic murine NK receptor, Ly49A, we show that the membrane proximal nonligand binding ecto-domain (the stalk region) is critical to ligand binding ..
  28. Leavenworth J, Pauza M. Engagement of transgenic Ly49A inhibits mouse CD4 cell activation by disrupting T cell receptor, but not CD28, signaling. Cell Immunol. 2009;257:88-96 pubmed publisher
    ..Engagement of transgenic Ly49A inhibits CD4 cell activation and delays onset of T1D in mice...
  29. Scarpellino L, Oeschger F, Guillaume P, Coudert J, Lévy F, Leclercq G, et al. Interactions of Ly49 family receptors with MHC class I ligands in trans and cis. J Immunol. 2007;178:1277-84 pubmed
    The Ly49A NK cell receptor interacts with MHC class I (MHC-I) molecules on target cells and negatively regulates NK cell-mediated target cell lysis...
  30. Doucey M, Scarpellino L, Zimmer J, Guillaume P, Luescher I, Bron C, et al. Cis association of Ly49A with MHC class I restricts natural killer cell inhibition. Nat Immunol. 2004;5:328-36 pubmed
    ..Here we show that the inhibitory Ly49A NK cell receptor not only binds to its H-2D(d) ligand expressed on potential target cells (in trans) but also is ..
  31. Brodin P, Lakshmikanth T, Kärre K, Höglund P. Skewing of the NK cell repertoire by MHC class I via quantitatively controlled enrichment and contraction of specific Ly49 subsets. J Immunol. 2012;188:2218-26 pubmed publisher
  32. Ebihara T, Jonsson A, Yokoyama W. Natural killer cell licensing in mice with inducible expression of MHC class I. Proc Natl Acad Sci U S A. 2013;110:E4232-7 pubmed publisher
    ..These data indicate that trans interaction with MHC class I on hematopoietic cells regulates NK-cell licensing, which is not associated with other obvious phenotypic changes. ..
  33. 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. ..
  34. McQueen K, Freeman J, Takei F, Mager D. Localization of five new Ly49 genes, including three closely related to Ly49c. Immunogenetics. 1998;48:174-83 pubmed
    ..Furthermore, in contrast to Ly49a, extensive variation in the arrangement and number of Ly49c-related genes in different mouse strains was observed...
  35. Chan P, Takei F. Molecular cloning and characterization of a novel murine T cell surface antigen, YE1/48. J Immunol. 1989;142:1727-36 pubmed
    ..Interestingly, YE1/48 expression appears to be induced in pre-B cells after transformation by Abelson virus, suggesting an association of YE1/48 expression with the transformation of T and pre-B Cells. ..
  36. Yokoyama W. Hybrid resistance and the Ly-49 family of natural killer cell receptors. J Exp Med. 1995;182:273-7 pubmed
  37. Yokoyama W. Natural killer cell receptors specific for major histocompatibility complex class I molecules. Proc Natl Acad Sci U S A. 1995;92:3081-5 pubmed
  38. Daniels B, Nakamura M, Rosen S, Yokoyama W, Seaman W. Ly-49A, a receptor for H-2Dd, has a functional carbohydrate recognition domain. Immunity. 1994;1:785-92 pubmed
    ..These results indicate that Ly-49A has a functional carbohydrate recognition domain and that target expression of carbohydrates alters their susceptibility to natural killing. ..
  39. 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. ..
  40. Held W, Raulet D. Ly49A transgenic mice provide evidence for a major histocompatibility complex-dependent education process in natural killer cell development. J Exp Med. 1997;185:2079-88 pubmed
    ..The formation of the Ly49 receptor repertoire was examined with transgenic mice that express Ly49A in all NK cells...
  41. 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
    ..Our genetic analysis suggests Chok is a single locus that affects NK cell-mediated cytotoxicity similar to other NKC loci that also regulate the complex activity of NK cells. ..
  42. 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. ..
  43. Scalzo A, Brown M, Chu D, Heusel J, Yokoyama W, Forbes C. Development of intra-natural killer complex (NKC) recombinant and congenic mouse strains for mapping and functional analysis of NK cell regulatory loci. Immunogenetics. 1999;49:238-41 pubmed
  44. Back J, Chalifour A, Scarpellino L, Held W. Stable masking by H-2Dd cis ligand limits Ly49A relocalization to the site of NK cell/target cell contact. Proc Natl Acad Sci U S A. 2007;104:3978-83 pubmed
    b>Ly49A is an inhibitory receptor, which counteracts natural killer (NK) cell activation on the engagement with H-2D(d) (D(d)) MHC class I molecules (MHC-I) on target cells...
  45. Andersson K, Williams G, Davis D, Höglund P. Quantifying the reduction in accessibility of the inhibitory NK cell receptor Ly49A caused by binding MHC class I proteins in cis. Eur J Immunol. 2007;37:516-27 pubmed
    ..Here, we establish that the number of transferred MHC class I proteins is proportional to the number of Ly49A receptors at the NK cell surface...
  46. 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
    ..In contrast, NK cell inhibition by the MHC class I-specific receptor Ly49A was independent of Fyn, suggesting that Fyn is specifically required for NK cell activation via non-MHC receptor(s)..
  47. Rouhi A, Gagnier L, Takei F, Mager D. Evidence for epigenetic maintenance of Ly49a monoallelic gene expression. J Immunol. 2006;176:2991-9 pubmed
    ..In this study, we show that hypomethylation of the region encompassing the Pro-2 promoter of Ly49a and Ly49c in primary C57BL/6 NK cells correlates with expression of the gene...
  48. Forbes C, Brown M, Cho R, Shellam G, Yokoyama W, Scalzo A. The Cmv1 host resistance locus is closely linked to the Ly49 multigene family within the natural killer cell gene complex on mouse chromosome 6. Genomics. 1997;41:406-13 pubmed
    ..4 map units. Furthermore, Cmv1 maps distal to, but very closely linked to, the Ly49 multigene family (< 0.2 map units), suggesting that MCMV resistance may be conferred by MHC class I-specific NK cell receptors. ..
  49. Choi T, Ferris S, Matsumoto N, Poursine Laurent J, Yokoyama W. Ly49-dependent NK cell licensing and effector inhibition involve the same interaction site on MHC ligands. J Immunol. 2011;186:3911-7 pubmed publisher
    ..quot; For example, Ly49A(+) NK cells become licensed by the interaction of the Ly49A inhibitory receptor with its MHC class I ligand, H2D(d)..
  50. Proteau M, Rousselle E, Makrigiannis A. Mapping of the BALB/c Ly49 cluster defines a minimal natural killer cell receptor gene repertoire. Genomics. 2004;84:669-77 pubmed
  51. Andrews D, Sullivan L, Baschuk N, Chan C, Berry R, Cotterell C, et al. Recognition of the nonclassical MHC class I molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells. Nat Immunol. 2012;13:1171-7 pubmed publisher
    ..Here we found that the prototypic inhibitory receptor Ly49A bound the highly conserved nonclassical MHC class I molecule H2-M3 with an affinity similar to its affinity for H-..
  52. Matsumoto N, Tajima K, Mitsuki M, Yamamoto K. H-2 allele specificity of the NK cell C-type lectin-like MHC class I receptor Ly49A visualized by soluble Ly49A tetramer. Int Immunol. 2001;13:615-23 pubmed
    b>Ly49A is a C-type lectin-like receptor on NK cells that recognizes MHC class I ligands, H-2D(d) and D(k). The engagement of Ly49A with the ligands inhibits activation of NK cells and protects target cells from lysis by NK cells...
  53. 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...
  54. Depatie C, Muise E, Lepage P, Gros P, Vidal S. High-resolution linkage map in the proximity of the host resistance locus Cmv1. Genomics. 1997;39:154-63 pubmed
    ..9)-D6Mit336-(2.2)- D6Mit218-(1.0)-D6Mit52-(0.5)-D6Mit194-(0.2)-Nkrp 1/ D6Mit61/135/257/289/338-(0.4)-Cmv1/Ly49A/D6Mit370++ +- (0.3)-Prp/Kap/D6Mit13/111/219-(0.3)-Tel/D6Mit374/290/ 220/196/195/110-(1.1)-D6Mit25...
  55. Regunathan J, Chen Y, Wang D, Malarkannan S. NKG2D receptor-mediated NK cell function is regulated by inhibitory Ly49 receptors. Blood. 2005;105:233-40 pubmed
    ..even a higher expression of H60 molecule on the target cells failed to overcome the inhibition mediated by Ly49A/G receptors...