IMMUNOGENETICS OF NATURAL KILLER RECEPTORS

• Project/Area Number: 14370111
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: HOKKAIDO UNIVERSITY (2004); The Graduate University for Advanced Studies (2002-2003)
• Principal Investigator: KASAHARA Masanori Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (30241318)
• Project Period (FY): 2002 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥11,700,000 (Direct Cost: ¥11,700,000); Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2003: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
• Keywords: Natural killer receptors / KIR / IgA Fc receptors / Ly49 / Leukocyte receptor complex / IgA Fc レセプター / LY49 / ウマ / leukocyte receptor complex / NKレセプター / MILL分子

Research Abstract

The aims of this project were to study the structure, function and evolution of natural killer (NK) receptors and their ligands using multidisciplinary approaches such as immunogenetics, comparative genomics and immunobiology. Major research accomplishments were as follows :
1.In humans, killer immunoglobulin (Ig)-like receptors (KIR) function as major NK receptors for HLA class I molecules. The genes coding for KIR are located in the region known as the leukocyte receptor complex (LRC). In mice, however, the LRC does not contain any KIR genes. For this reason, it has been assumed that mice lack KIR genes. Contrary to this widely-held belief, we identified two KIR-like genes on mouse chromosome X. These genes were named Kirl (KIR-like).
2.We found that mice do not have the IgA Fc receptor gene (Fcar), the human and rat counterparts of which map to the LRC. This observation, along with others, indicated that the genomic organization of the LRC differs substantially among mammalian species.
3.We have found that the horse has multiple Ly49 genes but no functional KIR genes, indicating that Ly49 are also used as NK receptors in mammals other than rodents.
4.We have identified a family of hagfish genes with features characteristic of paired Ig-like receptors. The V domain of this family shows substantial sequence similarity to that of T-cell and B-cell receptors. Hence, this family, which may function as NK receptors, was named "agnathan paired receptors resembling antigen receptors (APAR)".

Research Products

• [Journal Article] Hagfish leukocytes express a paired receptor family with a variable domain resembling those of antigen receptors (2005)
  • Author(s): Suzuki, T
  • Journal Title: J.Immunol. 174 Pages: 2885-2891
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Human testicular protein TPX1/CRISP-2 : localization in spermatozoa, fate after capacitation and relevance for gamete interaction (2005)
  • Author(s): Busso, D
  • Journal Title: Mol.Hum.Reprod 11
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Hagfish leukocytes express a paired receptor family with a variable domain resembling those of antigen receptors. (2005)
  • Author(s): Suzuki, T., Shin-I, T., Fujiyama, A., Kohara, Y, Kasahara, M.
  • Journal Title: J.Immunol. 174 Pages: 2885-2891
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Human testicular protein TPX1/CRISP-2 : localization in spermatozoa, fate after capacitation and relevance for gamete interaction. (2005)
  • Author(s): Busso, D., Cohen, D.J., Hayashi, M., Kasahara, M, Cuasnicu, P.S.
  • Journal Title: Mol.Hum.Reprod. 11
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Hagfish leukocytes express a paired receptor family with a variable domain resembling those of antigen receptors (2005)
  • Author(s): Suzuki T, et al.
  • Journal Title: J.Immunol 174 Pages: 2885-2891
• [Journal Article] Human testicular protein TPX1/CRISP-2 : localization in spermatozoa, fate after capacitation and relevance for gamete interaction (2005)
  • Author(s): Busso D, et al.
  • Journal Title: Mol.Hum.Reprod 11
• [Journal Article] On the origins of the adaptive immune system : novel insights from protochordates and cold-blooded vertebrates (2004)
  • Author(s): Kasahara, M
  • Journal Title: Trends Immunol 25 Pages: 105-111
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Natural killer cell receptors in the horse : evidence for the existence of multiple transcribed Ly49 genes (2004)
  • Author(s): Takahashi, T
  • Journal Title: Eur.J.Immunol 34 Pages: 773-784
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of the rat IgA Fc receptor encoded in the leukocyte receptor complex (2004)
  • Author(s): Maruoka, T
  • Journal Title: Immunogenetics 55 Pages: 712-716
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Comparative genomics of the Mill family : a rapidly evolving MHC class I gene family (2004)
  • Author(s): Watanabe, Y
  • Journal Title: Eur.J.Immunol 34 Pages: 1597-1607
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Transcriptome analysis of hagfish leukocytes : A framework for understanding the immune system of jawless fishes (2004)
  • Author(s): Suzuki, T
  • Journal Title: Dev.Comp.Immunol 28 Pages: 993-1003
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Construction of a bacterial artificial chromosome library from the inshore hagfish, Eptatretus burgeri : A resource for the analysis of the agnathan genome (2004)
  • Author(s): Suzuki, T
  • Journal Title: Genes Genet.Syst 79 Pages: 251-253
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] On the origins of the adaptive immune system : novel insights from protochordates and cold-blooded vertebrates. (2004)
  • Author(s): Kasahara, M., Suzuki, T, Du Pasquier, L.
  • Journal Title: Trends Immunol. 25 Pages: 105-111
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Natural killer cell receptors in the horse : evidence for the existence of multiple transcribed Ly49 genes. (2004)
  • Author(s): Takahashi, T., Yawata, M., Raudsepp, T., Lear, T.L., Chowdhary, B.P., Antczak, D.F, Kasahara, M.
  • Journal Title: Eur.J.Immunol. 34 Pages: 773-784
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of the rat IgA Fc receptor encoded in the leukocyte receptor complex. (2004)
  • Author(s): Maruoka, T., Nagata, T, Kasahara, M.
  • Journal Title: Immunogenetics 55 Pages: 712-716
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Comparative genomics of the Mill family : a rapidly evolving MHC class I gene family. (2004)
  • Author(s): Watanabe, Y., Maruoka, T., Walter, L, Kasahara, M.
  • Journal Title: Eur.J.Immunol. 34 Pages: 1597-1607
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Transcriptome analysis of hagfish leukocytes : A ework for understanding the immune system of jawless fishes. (2004)
  • Author(s): Suzuki, T., Shin-I, T., Kohara, Y, Kasahara, M.
  • Journal Title: Dev.Comp.Immunol. 28 Pages: 993-1003
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Construction of a bacterial artificial chromosome library from the inshore hagfish, Eptatretus burgeri : A resource for the analysis of the agnathan genome. (2004)
  • Author(s): Suzuki, T., Ota, T., Fujiyama, A, Kasahara, M.
  • Journal Title: Genes Genet.Syst. 79 Pages: 251-253
  • NAID: 130000062136
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] On the origins of the adaptive immune system : novel insights from protochordates and cold-blooded vertebrates. (2004)
  • Author(s): Kasahara, M, et al.
  • Journal Title: Trends Immunol 25 Pages: 105-111
• [Journal Article] Natural killer cell receptors in the horse : evidence for the existence of multiple transcribed Ly49 genes (2004)
  • Author(s): Takahashi T, et al.
  • Journal Title: Eur.J.Immunol 34 Pages: 773-784
• [Journal Article] Identification of the rat IgA Fc receptor encoded in the leukocyte receptor complex (2004)
  • Author(s): Maruoka T, et al.
  • Journal Title: Immunogenetics 55 Pages: 712-716
• [Journal Article] Comparative genomics of the Mill family : a rapidly evolving MHC class I gene family (2004)
  • Author(s): Watanabe Y, et al.
  • Journal Title: Eur.J.Immunol 34 Pages: 1597-1607
• [Journal Article] Transcriptome analysis of hagfish leukocytes : A framework for understanding the immune system of jawless fishes (2004)
  • Author(s): Suzuki T, et al.
  • Journal Title: Dev.Comp.Immunol 28 Pages: 993-1003
• [Journal Article] Construction of a bacterial artificial chromosome library from the inshore hagfish, Eptatretus burgeri : A resource for the analysis of the (2004)
  • Author(s): Suzuki T, et al.
  • Journal Title: Genes Genet.Syst 79 Pages: 251-253
• [Journal Article] Identification of the mouse killer immunoglobulin-like receptor-like (Kirl) gene family mapping to chromosome X (2003)
  • Author(s): Welch, A
  • Journal Title: Immunogenetics 54 Pages: 782-790
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genomic analysis of immunity in a basal chordate and the emergence of the vertebrate immune system : Waiting for Godot (2003)
  • Author(s): Azumi, K
  • Journal Title: Immunogenetics 55 Pages: 570-581
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of the mouse killer immunoglobulin-like receptor-like (Kirl) gene family mapping to chromosome X. (2003)
  • Author(s): Welch, A.Y., Kasahara, M, Spain, L.M.
  • Journal Title: Immunogenetics 54 Pages: 782-790
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genomic analysis of immunity in a basal chordate and the emergence of the vertebrate immune system : Waiting for Godot. (2003)
  • Author(s): Azumi, K., De Santis, R., De Tomaso, A., Rigoutsos, I., Yoshizaki, F., Pinto, M.R., Marino, R., Shida, K., Ikeda, M., Shimizu, T., Ikeda, M., Arai, M., Inoue, Y., Satoh, N., Rokhsar, D.S., Du Pasquier, L., Kasahara, M., Satake, M, Nonaka, M.
  • Journal Title: Immunogenetics 55 Pages: 570-581
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A family of NHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex (2002)
  • Author(s): Kasahara, M
  • Journal Title: Proc.Natl.Acad.Sci.USA 99 Pages: 13687-13692
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The leukocyte common antigen (CD45) of the Pacific hagfish, Eptatretus stoutii : implications for the primordial function of CD45 (2002)
  • Author(s): Nagata, T
  • Journal Title: Immunogenetics 54 Pages: 286-291
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Xenopus class II A genes : studies of genetics, polymorphism, and expression (2002)
  • Author(s): Liu, Y
  • Journal Title: Dev.Comp.Immunol 26 Pages: 735-750
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex. (2002)
  • Author(s): Kasahara, M.
  • Journal Title: Proc.Natl.Acad.Sci.USA 99 Pages: 13687-13692
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The leukocyte common antigen (CD45) of the Pacific hagfish, Eptatretus stoutii implications for the primordial function of CD45. (2002)
  • Author(s): Nagata, T., Suzuki, T., Ohta, Y., Flajnik, M.F, Kasahara, M.
  • Journal Title: Immunogenetics 54 Pages: 286-291
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Xenopus class II A genes : studies of genetics, polymorphism, and expression. (2002)
  • Author(s): Lin, Y., Kasahara, M., Rumfelt, L.L, Flajnik, M.F.
  • Journal Title: Dev.Comp.Immunol. 26 Pages: 735-750
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Nature Encyclopedia of the Human Genome, Vol.4 (Cooper (ed.)) (2003)
  • Author(s): Kasahara, M
  • Total Pages: 5
  • Publisher: Nature Publishing Group, Macmillan Publishers Ltd
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Welch, A.Y.et al.: "Identification of the mouse killer immunoglobulin-like receptor-like (Kirl) gene family mapping to chromosome X."Immunogenetics. 54. 782-790 (2003)
• [Publications] Azumi, K. et al.: "Genomic analysis of immunity in a basal chordate and the emergence of the vertebrate immune system : Waiting for Godot."Immunogenetics. 55. 570-581 (2003)
• [Publications] Kasahara, M. et al.: "On the origins of the adaptive immune system : novel insights from protochordates and cold-blooded vertebrates."Trends Immunol.. 25. 105-111 (2004)
• [Publications] Maruoka, T. et al.: "Identification of the rat IgA Fc receptor encoded in the leukocyte receptor complex."Immunogenetics. 55. 712-716 (2004)
• [Publications] Takahashi, T. et al.: "Natural killer cell receptors in the horse : evidence for the existence of multiple transcribed Ly49 genes."Eur.J.Immunol.. 34. 773-784 (2004)
• [Publications] Kasahara, M.: "Polyploid origin of the human genome. In : D. N. Cooper (ed.) : Nature Encyclopedia of the Human Genome, Vol. 4"Nature Publishing Group, Macmillan Publishers Ltd.. 5 (2003)
• [Publications] Kasahara, M.: "MHC genomics : from the proteasome to genome evolution. In : H. -G. Rammensee and R. Dawkins (eds.) : Antigen Processing - Mechanisms, Genomics and Evolution"Wiley-VCH(印刷中). (2004)
• [Publications] Kasahara, M., et al.: "A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex"Proc. Nati. Acad. Sci. USA. 99. 13687-13692 (2002)
• [Publications] Nagata, T., et al.: "The leukocyte common antigen (CD45) of the Pacific hagfish, Eptatretus stoutii : implications for the primordial function of CD45"Immunogenetics. 54. 286-291 (2002)
• [Publications] Liu, Y., et al.: "Xenopus class II A genes : studies of genetics, polymorphism, and expression"Dev. Comp. Immunol. 26. 735-750 (2002)
• [Publications] Welch, A.Y., et al.: "Identification of the mouse killer immunoglobulin-like receptor-like (Kirl) gene family mapping to chromosome X"Immunogenetics. 54. 782-790 (2003)
• [Publications] Kasahara, M.: "Polyploid origin of the human genome. In : D.N.Cooper(ed.) : Encyclopedia of the Human Genome"Nature Publishing Group(印刷中). (2003)