Ligand for herpes simplex virus entry mediator and methods of use

Abstract

A novel polypeptide ligand, p30, or LIGHT, for herpes virus entry mediator, HVEM, is provided. LIGHT is useful for modulating immune responses and in inhibiting infection and/or subsequent proliferation by herpesvirus. HVEM fusion proteins are also provided. Methods for treating subjects with lymphoid cell disorders, tumors, autoimmune diseases, inflammatory disorders or those having or suspected of having a herpesvirus infection, utilizing p30 and the fusion proteins of the invention, are also provided.

1 . An isolated or recombinant homotrimeric p30 polypeptide comprising a monomer polypeptide having an apparent molecular weight of about 30 kDa, wherein the homotrimeric polypeptide binds to a herpes virus entry mediator (HVEM) polypeptide or a lymphotoxin β receptor (LTβR) polypeptide under physiologic conditions. 
     
     
         2 . The isolated or recombinant homotrimeric p30 polypeptide of  claim 1 , wherein the monomer polypeptide comprises isomers having a pI from about 7 to about 8.5. 
     
     
         3 . A soluble isolated or recombinant homotrimeric p30 polypeptide lacking a transmembrane domain, wherein the soluble homotrimeric polypeptide binds to a herpes virus entry mediator (HVEM) polypeptide or a lymphotoxin β receptor (LTβR) polypeptide under physiologic conditions. 
     
     
         4 .- 25 . (canceled) 
     
     
         26 . A method for inhibiting a p30 polypeptide-mediated cellular response comprising
 (a) providing a composition that inhibits binding of a cell surface expressed p30 polypeptide to a cell surface expressed HVEM or LTβR, and   (b) contacting the cell expressing the cell surface expressed p30 polypeptide or the cell surface expressed HVEM or LTβR with an amount of the composition sufficient to inhibit a p30 polypeptide-mediated cellular response.   
     
     
         27 . The method of  claim 26 , wherein the cell is contacted with the composition in vivo. 
     
     
         28 . The method of  claim 26 , wherein the inhibited p30 polypeptide-mediated cellular response comprises inhibition of a lymphocyte cellular response. 
     
     
         29 . The method of  claim 28 , wherein the inhibited lymphocyte response is lymphocyte proliferation. 
     
     
         30 . The method of  claim 28 , wherein the inhibited lymphocyte is a pathogenic effector cell. 
     
     
         31 . The method of  claim 28 , wherein the inhibited lymphocyte response modulates a T or a B lymphoma or leukemia or an autoimmune disease. 
     
     
         32 .- 36 . (canceled) 
     
     
         37 . The method of  claim 26 , wherein the contacted cell expresses p30 polypeptide on its cell surface and the composition is an anti-p30 antibody. 
     
     
         38 . (canceled) 
     
     
         39 . A method of modulating a lymphotoxin beta receptor (LTβR)-mediated cellular response, the method comprising:
 (a) providing a composition that inhibits binding of an LTβR to a p30 polypeptide; and 
 (b) contacting a cell expressing the LTβR or the p30 polypeptide with an amount of the composition sufficient to modulate the lymphotoxin β receptor (LTβR)-mediated cellular response. 
 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 39 , wherein the cell expresses a p30 polypeptide and the composition comprises an anti-p30 antibody. 
     
     
         42 .- 95 . (canceled)