Methods For Detecting Th1 Cells

Abstract

The inventors discovered that the adhesion molecule CAR, known to be localized in intracellular adhesion sites, functioned as an adhesion molecule for activated lymphocytes. Further, the inventors identified CARL, a novel CAR ligand expressed in lymphocytes, and clarified that the ligand was expressed selectively in Th1 cells. In addition, they found that anti-CAR antibodies could inhibit the adhesion of activated lymphocytes to CAR molecules. Thus, the present invention provides methods for detecting Th1 cells using CAR or anti-CARL antibodies, and methods of screening for inhibitors suppressing the adhesion of Th1 cells using the binding between CAR and CARL as an index. Furthermore, the present invention relates to methods of screening for inhibitors of the binding between CAR and CARL, antibodies that inhibit the binding between CAR and CARL, and therapeutic compositions comprising these antibodies. These are expected to be useful in diagnosing diseases, such as inflammation, in which infiltration of Th1 cells is involved, and in providing pharmaceutical agents for alleviating such diseases.

1 .- 8 . (canceled) 
     
     
         9 . A kit for detecting a Th1 cell, which comprises an anti-CARL antibody as a detection reagent. 
     
     
         10 . The kit of  claim 9 , wherein the anti-CARL antibody is bound to a carrier. 
     
     
         11 . The kit of  claim 9  that determines whether a subject from whom a cell sample is collected is affected with an atopic disease. 
     
     
         12 .- 14 . (canceled) 
     
     
         15 . An antibody that inhibits the binding between a CAR and a CARL, wherein a CARL is a protein of any one of:
 (1) a protein comprising the amino acid sequence of SEQ ID NO: 1;   (2) a protein comprising an extracellular domain of the amino acid sequence of SEQ ID NO: 1;   (3) a protein comprising the amino acid sequence of SEQ ID NO: 2;   (4) a protein comprising an extracellular domain of the amino acid sequence of SEQ ID NO: 2;   (5) a protein comprising an Ig-like domain 1 of an amino acid sequence of an above (1) to (4);   (6) a protein encoded by a polynucleotide that hybridizes under stringent conditions to the cDNA sequence of SEQ ID NO: 3 or 4;   (7) a protein comprising an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to a polynucleotide encoding an amino acid sequence of a protein of an above (1) to (5);   (8) a protein comprising an amino acid sequence with 90% or more homology to an amino acid sequence of a protein of an above (1) to (5); or   (9) a protein comprising an amino acid sequence with a deletion, substitution, addition, or insertion of one or more amino acid residues in the amino acid sequence of a protein of an above (1) to (5).   
     
     
         16 . The antibody of  claim 15 , wherein the CAR and the CARL are derived from a human. 
     
     
         17 .- 18 . (canceled) 
     
     
         19 . The antibody of  claim 15  or  16 , wherein the antibody is an anti-CARL antibody. 
     
     
         20 . The antibody of  claim 19 , wherein the anti-CARL antibody is produced by hybridoma @mCARL:#3.11 deposited under Accession Number: FERM BP-10319. 
     
     
         21 . A cell adhesion inhibitor comprising the antibody of  claim 15 . 
     
     
         22 . A therapeutic agent for contact dermatitis, which comprises the antibody of  claim 15 .