Activity modulator, medicinal agent comprising same, use of cd300a gene-deficient mouse, and anti-cd300a antibody

Abstract

The present invention aims to provide: an immunostimulant useful for maintaining, enhancing or suppressing an immune function associated with CD300a activation signaling, or an immunomodulator as an immunosuppressant useful for suppressing the immune function; use of a CD300a gene-deficient mouse for pathology analysis and the like; an anti-CD300a antibody; and the like.

What is claimed is: 
     
         1 . A method for treatment of a disease or disease state in which inhibitory signal transduction of a cluster of differentiation 300a (CD300a)-expressing myeloid cell is involved, comprising:
 administering an effective amount of phosphatidyl serine,   wherein said phosphatidyl serine promotes inhibitory signal transduction of a CD300a-expressing myeloid cell.   
     
     
         2 . The method for treatment according to  claim 1 , wherein said disease is an inflammatory infection, allergic disease or autoimmune disease. 
     
     
         3 . The method for treatment according to  claim 1 , wherein said disease is celiac disease. 
     
     
         4 . A method for carrying out pathology analysis of atopic dermatitis, inflammatory bowel disease or asthma comprising use of a cluster of differentiation 300a (CD300a) gene-deficient mouse to which has been administered a substance that induces atopic dermatitis, inflammatory bowel disease or asthma as a model mouse that hardly develops atopic dermatitis, inflammatory bowel disease or asthma after administration of a substance that induces atopic dermatitis, inflammatory bowel disease or asthma. 
     
     
         5 . The method for carrying out pathology analysis according to  claim 4 ,
 wherein said substance that induces atopic dermatitis is mite antigen or ovalbumin,   wherein said substance that induces inflammatory bowel disease is dextran sodium sulfate, and   wherein said substance that induces asthma is mite antigen or ovalbumin.   
     
     
         6 . A method for screening a candidate substance for efficacy in the treatment or prophylaxis of celiac disease, said method comprising:
 i) administering said candidate substance to a cluster of differentiation 300a (CD300a) gene-deficient mouse in which celiac disease has been induced following the administration to said mouse of a substance that induces celiac disease, and determining the presence or absence of a therapeutic effect; or   ii) administering said candidate substance with a substance that induces celiac disease to a CD300a gene-deficient mouse, and determining the presence or absence of a prophylactic effect.   
     
     
         7 . The method of  claim 6 , wherein said substance that induces celiac disease is a gluten-derived gliadin peptide. 
     
     
         8 . An anti-human cluster of differentiation 300a (CD300a) antibody comprising:
 i) an H-chain variable region having the amino acid sequence of SEQ ID NO: 19 or an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 19 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 19; and   ii) an L-chain variable region having the amino acid sequence of SEQ ID NO: 20 or an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 20 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 20.   
     
     
         9 . An anti-mouse cluster of differentiation 300a (CD300a) antibody comprising:
 i) an H-chain variable region having the amino acid sequence of SEQ ID NO: 17 or an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 17 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 17; and   ii) an L-chain variable region having the amino acid sequence of SEQ ID NO: 18 or an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 18 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 18.   
     
     
         10 . A method of manufacturing a pharmaceutical composition, the method comprising:
 mixing the anti-human cluster of differentiation 300a (CD300a) antibody of  claim 8  with a pharmaceutically acceptable carrier.   
     
     
         11 . An anti-human cluster of differentiation 300a (CD300a) antibody comprising:
 i) an H-chain variable region having an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 19 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 19; and   ii) an L-chain variable region having an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 20 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 20.   
     
     
         12 . An anti-mouse cluster of differentiation 300a (CD300a) antibody comprising:
 i) an H-chain variable region having an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 17 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 17; and   ii) an L-chain variable region having or an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 18 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in a region other than the complementarity determining regions of SEQ ID NO: 18.   
     
     
         13 . A method for treatment of a disease or disease state in which inhibitory signal transduction of a cluster of differentiation 300a (CD300a)-expressing myeloid cell is involved via an immunoreceptor tyrosine-based inhibitory motif (ITIM) of CD300a, comprising:
 administering to a subject an effective amount of a neutralizing antibody against CD300a which inhibits binding between CD300a and phosphatidyl serine;   wherein said neutralizing antibody against CD300a suppresses inhibitory signal transduction of the CD300a-expressing myeloid cell, and
 wherein said neutralizing antibody against CD300a is: 
 an anti-human CD300a antibody comprising: 
 i) an H-chain variable region having the amino acid sequence of SEQ ID NO: 19 or an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 19 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in the complementarity determining regions of SEQ ID NO: 19; and 
 ii) an L-chain variable region having the amino acid sequence of SEQ ID NO: 20 or an amino acid sequence that is the same as the amino acid sequence of SEQ ID NO: 20 except that 1, 2, 3, 4, or 5 amino acid(s) is/are each substituted, added, inserted or deleted in the complementarity determining regions of SEQ ID NO: 20.