Lymphocyte homing receptors

Abstract

DNA isolates coding for the lymphocyte homing receptor and methods of obtaining such DNA are provided, together with expression systems for recombinant production of the lymphocyte homing receptor useful in therapeutic or diagnostic compositions.

1 - 2 . (canceled)  
     
     
         3 . An isolated polypeptide encoded by a DNA able to hybridize under stringent conditions to the complement of a DNA sequence encoding the carbohydrate domain (Trp39 to Cys155), the epidermal growth factor domain (Cys160 to Leu193); or a complement binding domain (Cys197 to Glu328) of the leukocyte homing receptor (LHR) amino acid sequence shown in  FIG. 1  (SEQ ID NO:2), wherein the polypeptide is devoid of a functional cytoplasmic domain, and wherein the stringent hybridization conditions comprise 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardts solution, 10 % dextran sulfate, and 20 micrograms per ml denatured, sheared salmon sperm DNA, overnight at 42° C., and wherein said polypeptide has one or more of the following functional characteristics: 
 a) binds a known LHR ligand or anti-LHR antibody;    b) induces anti-LHR antibodies;    c) mediates binding of lymphocytes to endothelium of lymphoid tissue; or    d) competes with normal binding of lymphocytes to lymphoid tissue.    
     
     
         4 . An isolated polypeptide consisting essentially of an amino acid sequence that is at least 70% homologous to one or more of the carbohydrate binding domain (Trp39 to Cys155), the epidermal growth factor domain (Cys160 to Leu193), or a complement binding domain (Cys197 to Glu328) of the leukocyte homing receptor having the amino acid sequence of SEQ ID NO:2, and wherein said polypeptide has one or more of the following functional characteristics: 
 a) binds a known LHR ligand or anti-LHR antibody;    b) induces anti-LHR antibodies;    c) mediates binding of lymphocytes to endothelium of lymphoid tissue; or d) competes with normal binding of lymphocytes to lymphoid tissue.    
     
     
         5 . The polypeptide of  claim 4 , having the amino acid sequence spanning Trp39 to Cys155 of SEQ ID NO:2.  
     
     
         6 . The polypeptide of  claim 4 , having the amino acid sequence spanning Cys160 to Leu193 of SEQ ID NO:2.  
     
     
         7 . The polypeptide of  claim 4 , having the amino acid sequence spanning Cys197 to Glu328 of SEQ ID NO:2.  
     
     
         8 . An isolated polypeptide comprising an amino acid sequence that is at least 70% homologous to one or more of the carbohydrate binding domain (Trp39 to Cys155), the epidermal growth factor domain (Cys160 to Leu193), or a complement binding domain (Cys197 to Glu328) of the leukocyte homing receptor having the amino acid sequence of SEQ ID NO:2, wherein the polypeptide lacks a functional transmembrane domain, and wherein said polypeptide has one or more of the following functional characteristics: 
 a) binds a known LHR ligand or anti-LHR antibody;    b) induces anti-LHR antibodies;    c) mediates binding of lymphocytes to endothelium of lymphoid tissue; or d) competes with normal binding of lymphocytes to lymphoid tissue.    
     
     
         9 . An isolated polypeptide comprising an amino acid sequence that is at least 70% homologous to one or more of the carbohydrate binding domain (Trp39 to Cys 155), the epidermal growth factor domain (Cys160 to Leu193), or a complement binding domain (Cys197 to Glu328) of the leukocyte homing receptor having the amino acid sequence of SEQ ID NO:2, wherein the polypeptide lacks a functional cytoplasmic domain, and wherein said polypeptide has one or more of the following functional characteristics: 
 a) binds a known LHR ligand or anti-LHR antibody;    b) induces anti-LHR antibodies;    c) mediates binding of lymphocytes to endothelium of lymphoid tissue; or    d) competes with normal binding    
     
     
         10 . An isolated polypeptide encoded by a DNA able to hybridize under stringent conditions to the complement of a DNA sequence encoding the carbohydrate binding domain (Trp39 to Cys155), the epidermal growth factor domain (Cys160 to Leu193); or a complement binding domain (Cys197 to Glu328) of the leukocyte homing receptor (LHR) amino acid sequence shown in  FIG. 1  (SEQ ID NO:2), wherein the stringent conditions are overnight incubation at 42° C. in a solution comprising 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardts solution, 10 % dextran sulfate, and 20 micrograms per ml denatured, sheared salmon sperm DNA, and wherein the polypeptide lacks a functional transmembrane domain, a functional cytoplasmic domain, or both, and wherein said polypeptide has one or more of the following functional characteristics: 
 a) binds a known LHR ligand or anti-LHR antibody;    b) induces anti-LHR antibodies;    c) mediates binding of lymphocytes to endothelium of lymphoid tissue; or    d) competes with normal binding of lymphocytes to lymphoid tissue.    
     
     
         11 . An isolated polypeptide encoded by a DNA able to hybridize under stringent conditions to the complement of a DNA sequence encoding the carbohydrate binding domain (Trp39 to Cys155), the epidermal growth factor domain (Cys160 to Leu193); or a complement binding domain (Cys197 to Glu328) of the leukocyte homing receptor (LHR) amino acid sequence shown in  FIG. 1  (SEQ ID NO:2), wherein the polypeptide is devoid of a functional transmembrane domain, and wherein the stringent conditions are overnight incubation at 42° C. in a solution comprising 20% formamide, 5×SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardts solution, 10 % dextran sulfate, and 20 micrograms per ml denatured, sheared salmon sperm DNA, and wherein said polypeptide has one or more of the following functional characteristics: 
 a) binds a known LHR ligand or anti-LHR antibody;    b) induces anti-LHR antibodies;    c) mediates binding of lymphocytes to endothelium of lymphoid tissue; or    d) competes with normal binding of lymphocytes to lymphoid tissue.