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WO2004048574A1 - Proteines d'immunorecepteurs - Google Patents

Proteines d'immunorecepteurs Download PDF

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Publication number
WO2004048574A1
WO2004048574A1 PCT/JP2003/014929 JP0314929W WO2004048574A1 WO 2004048574 A1 WO2004048574 A1 WO 2004048574A1 JP 0314929 W JP0314929 W JP 0314929W WO 2004048574 A1 WO2004048574 A1 WO 2004048574A1
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WO
WIPO (PCT)
Prior art keywords
protein
mair
immunoreceptor
cells
dna
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PCT/JP2003/014929
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English (en)
Japanese (ja)
Inventor
Akira Shibuya
Original Assignee
Riken
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Riken filed Critical Riken
Priority to AU2003284432A priority Critical patent/AU2003284432A1/en
Publication of WO2004048574A1 publication Critical patent/WO2004048574A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Definitions

  • the present invention relates to a novel immunoreceptor protein, a gene encoding the protein, a recombinant vector containing the gene, a transformant containing the recombinant vector, a method for producing the protein, and the like.
  • the activated immune cells bind to the immunoreceptor tyrosine-based inhibitory motif (Immunoreceptor tyrosine-based inhibitor), which is present in the intracellular region by binding the inhibitory cell membrane receptor molecule to the ligand.
  • B cells and / or myeloid cells are derived from human and mouse FCT receptors (Ravetch, JY & RA Clynes, Annu Rev Immunol, 16, 421-32, 1998; Daeron, M., Annur Rev Immunol, 15, 203-34, 1997), mouse pair immunoglobulin (Ig) -like receptor (PIR) (Kubagawa, H., et al., Proc Natl Acad Sci, USA, 94, 5261-5266, 1997; Hayami, K., et al., J Biol Chem, 272, 7320-7327, 1997) and its human homolog Ig-like transcript
  • FIG. 2A shows the results of lysing BW5147 cells expressing Flag-tagged MAIR-1 or MAIR-II, and immunoblotting the protein with anti-Flag mAb under reducing or non-reducing conditions.
  • FIG. 8 shows TNF- ⁇ production after transfection of the Flag-tagged MAIR-II gene-transformed transformant with an anti-Flag antibody.
  • FIG. 8 shows the production of TNF- ⁇ after cross-linking the MAIR-II molecule on peritoneal macrophages with an anti-MAIR-II antibody.
  • the nucleotide sequence of the gene of the present invention is determined, it is subsequently synthesized by chemical synthesis, by PCR using the cDNA of this gene as type III, or by hybridization using a DNA fragment having the nucleotide sequence as a probe, The gene of the present invention can be obtained.
  • test substance any substance can be used, and its type is not particularly limited.
  • test substances include, for example, peptides, proteins, non-peptidic compounds, synthetic compounds, natural product extracts (plant extracts, animal tissues and animal cell extracts), or compound libraries, phage display libraries or It may be a pinatorial library. Construction of a compound library is known to those skilled in the art, and a commercially available compound library can also be used.
  • test substance any substance can be used, and its type is not particularly limited.
  • test substances include, for example, peptides, proteins, non-peptidic compounds, synthetic compounds, natural product extracts (plant extracts, animal tissues and animal cell extracts), or compound libraries, phage display libraries or It may be a pinatorial library. Construction of compound libraries is known to those skilled in the art, and commercially available compound libraries can also be used.
  • the gene of the present invention When the gene of the present invention is used as a gene therapy agent for an immune system disease, a method of directly administering the gene of the present invention by injection and a method of administering a vector into which the gene has been incorporated can be mentioned.
  • the above vectors include adenovirus vector, adeno-associated virus vector, herpes virus vector, vaccinia virus vector, retrovirus vector, and the like.
  • the administration can be carried out efficiently by using a teratase.
  • a method of introducing the gene of the present invention into phospholipid vesicles such as ribosomes and administering the ribosome may be employed.
  • PCR was performed on 14-day-old fetal liver derived from wild-type and mouse strains lacking myeloid cells.
  • RDA subtractive hybridization
  • FIG. 1C shows a Southern plot analysis of the genomes MAIR-1 and MAIR-II.
  • Mouse genomic DNA was converted to restriction enzymes (E; Eco-RLB; Bam-HI, H; Hind-III, X; Xba-1, P;
  • Figures 4B, C, and D show spleen, bone marrow, or peritoneal macrophages derived from C57 / BL6 mice with anti-MAIR-1 (TX-8 mAb) or anti-MAIR-II (TX-13 mAb). ) And PE-bound mAb, followed by staining with arophycocynin (APC) -bound streptavidin. Analysis of spleen and bone marrow cells by flow cytometry showed that MAIR-1 was expressed on most myeloid cells, including macrophages, dendritic cells, granulocytes, marrow-derived mast cells, and some subsets of B cells. However, they were not expressed in T cells or NK cells (Fig.
  • 3H-serotonin-loaded mast cells were treated with 101 rat IgE anti-DNP mAb (25 g / ml) and various concentrations of rat anti-MAIR-1 or control IgG (IgE niAb + anti-MAIR-1 or IgE niAt) + control IgG), incubate for 30 minutes at 4 ° C, wash, and resuspend in 25 L medium. Suspended. Mast cells primed with the antibody were challenged with 25 / xl Fg (anti-rat) Ig F antibody (40 g / ml) F (alD ') 2 fragment for 30-60 minutes at 37 ° C. The reaction was stopped by adding cold PBS.
  • the transformant was dissolved in 1% digitonin buffer, the cell lysate was immunoprecipitated with control IgG, anti-DAP12 or anti-FcRIr, and the isolated protein was anti-MAIR-II.
  • the immunoblot was performed. As shown in Figure 7A, co-immunoprecipitation of MAIR-II and DAP12 was confirmed, and it was clear that MAIR-II was associated with MP12, but co-immunoprecipitation with FcsRI Not confirmed.
  • RAW cells expressing peritoneal macrophages derived from Flag-tagged MAIR-II or C57BL / 6 mice were pretreated with anti-CD32 / 16 (FcrR) and plastic-coated control IgG, anti-Flag or anti-FragR. -Stimulated with MAIR-II mAb and cultured for 48 hours.
  • the TNF- ⁇ concentration in the cell supernatant was measured using ELISA kit (e-Bioscience, San Diego, CA) according to the manufacturer's instructions.
  • the production of the inflammatory cytokine, TNF- ⁇ was significantly enhanced when cross-linked with an anti-Flag antibody.
  • SEQ ID NO: 9 synthetic thigh A
  • SEQ ID NO: 12 synthetic DNA

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Pulmonology (AREA)
  • Diabetes (AREA)
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  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
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  • Ophthalmology & Optometry (AREA)
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  • Obesity (AREA)
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Abstract

L'invention concerne de nouvelles protéines d'immunorécepteurs qui contrôlent positivement ou négativement les réponses immunitaires et les gènes codants pour ces protéines. Une protéine ayant la séquence d'acides aminés représentée par SEQ ID No:2 dans le listage de séquences ou une protéine ayant une séquence d'acides aminés dérivée de la séquence d'acides aminés susmentionnée par délétion, substitution ou addition d'au moins un acide aminé et ayant une fonction d'inhibition d'une réponse immunitaire de cellules ; une protéine ayant la séquence d'acides aminés représentée par SEQ ID Np:4 dans le listage de séquences ou une protéine ayant une séquence d'acides aminés dérivée de la séquence d'acides aminés susmentionnée par délétion, substitution ou addition d'au moins un acide aminé et ayant une fonction d'activation de la réponse immunitaire des cellules ; et enfin les gènes codants pour ces protéines.
PCT/JP2003/014929 2002-11-25 2003-11-21 Proteines d'immunorecepteurs WO2004048574A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003284432A AU2003284432A1 (en) 2002-11-25 2003-11-21 Immunoreceptor proteins

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002-341195 2002-11-25
JP2002341195A JP2004173531A (ja) 2002-11-25 2002-11-25 免疫受容体タンパク質

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9850309B2 (en) 2012-11-07 2017-12-26 University Of Tsukuba Medicament comprising activity modulator for CD300a-expressing cell associated with allergic disease, CD300a gene-deficient mouse, and use of activity modulator for CD300a-expressing cell
US10519233B2 (en) 2011-11-21 2019-12-31 University Of Tsukuba Activity modulator, medicinal agent comprising same, use of CD300A gene-deficient mouse, and anti-CD300A antibody

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
DATABASE GENBANK [online] 31 October 2002 (2002-10-31), YOSHIMOTO M. ET AL.: "Mus musculus mRNA for MMAC8", XP002976273, Database accession no. (AB065156) *
KUMAGAI H. ET AL.: "Idenitfication and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 307, no. 3, 1 August 2003 (2003-08-01), pages 719 - 729, XP004441488 *
LUO K. ET AL.: "DlgR1, a novel membrane receptor of the immunoglobulin gene superfamily is preferentially expressed by antigen-presenting cells", BIOCHEM. BIOPHYS. RES. COMMUN., vol. 287, no. 1, 2001, pages 35 - 41, XP002975879 *
VELY F. ET AL.: "Conservation of structural features reveals the existence of a large family of inhibitory cell surface receptors and noninhibitory/activatory counterparts", J. IMMUNOL., vol. 159, no. 5, 1997, pages 2075 - 2077, XP002106537 *
YOTSUMOTO K. ET AL.: "Paired activating and inhibitory immunoglobulin-like receptors MAIR-I and MAIR-II regulate mast cell and macrophage activation", J. EXP. MED., vol. 198, no. 2, 21 July 2003 (2003-07-21), pages 223 - 233, XP002975886 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10519233B2 (en) 2011-11-21 2019-12-31 University Of Tsukuba Activity modulator, medicinal agent comprising same, use of CD300A gene-deficient mouse, and anti-CD300A antibody
US9850309B2 (en) 2012-11-07 2017-12-26 University Of Tsukuba Medicament comprising activity modulator for CD300a-expressing cell associated with allergic disease, CD300a gene-deficient mouse, and use of activity modulator for CD300a-expressing cell

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Publication number Publication date
AU2003284432A1 (en) 2004-06-18
JP2004173531A (ja) 2004-06-24

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