Methods of modulation of the immune system

Abstract

Manipulation of the EphB6 receptor and its active Eph partners allow for regulation of T cell responses, including TCR signalling, T cell proliferation, and induction of T cell death. Methods of modulating EphB6 are described as well as various therapeutic applications.

1 - 22 . (canceled)  
   
   
       23 . A method of modulating apoptosis, said method comprising administering to the cell an effective amount of a substance that modulates EphB6 function, thereby modulating apoptosis.  
   
   
       24 . The method according to  claim 23 , wherein the substance that modulates EphB6 function is ephrin-B1, ephrin-B2, an antibody or a fragment thereof capable of binding EphB6, or an antisence molecule to EphB6.  
   
   
       25 . The method according to  claim 24  wherein the substance that modulates EphB6 function is Ephrin B1 or Ephrin B2.  
   
   
       26 . The method according to claims  23  wherein a substance which stimulates T-cell expression of EphB6 is co-administered.  
   
   
       27 . The method according to  claim 26 , wherein the substance which modulates T-cell expression of EphB6 is ephrin B1, ephrin B2, or a combination thereof.  
   
   
       28 . The method according to  claim 27  wherein the catalytically active member of the EphB subfamily is EphB1.  
   
   
       29 . The method according to  claim 23  wherein the substance that modulates T-cell expression of EphB6 is ephrin-B1, an EphB6 receptor, ephrin- B2, an antibody or an antibody fragment capable of binding EphB6, or an antisense molecule to EphB6.  
   
   
       30 . The method according to  claim 29 , wherein the substance that modulates T-cell expression of EphB6 is Ephrin-B1 or Eprin-B2.  
   
   
       31 . The method according to  claim 29 , wherein the T-cell is a human T-cell.  
   
   
       32 . A method of modulating cell proliferation, comprising administering to a population of cells comprising T-cells an effective amount of a substance which modulates EphB6 function.  
   
   
       33 . The method according to  claim 32 , wherein the substance that modulates EphB6 function is ephrin-B1, an antibody or fragment thereof capable of binding EphB6, or an antisense molecule to EphB6.  
   
   
       34 . The method according to  claim 32 , wherein the EphB6 function is further defined as T-cell EphB6 function of a human T-cell.  
   
   
       35 . The method according to  claim 32 , wherein the T-cell is a human T-cell.  
   
   
       36 . A method of modulating a T-cell response in an animal, comprising administering to the animal an effective amount of a substance that modulates T-cell expression of EphB6 such that the T-cell response is modulated.  
   
   
       37 . The method according to  claim 36 , wherein the substance that modulates T-cell expression of EphB6 is ephrin-B1, ephrin -B2, an antibody or antibody fragment capable of binding EphB6, or an antisense molecule to EphB6.  
   
   
       38 . The method according to  claim 37 , wherein the substance which modulates T-cell expression of EphB6 is Ephrin-B1 or Ephrin B2.  
   
   
       39 . The method according to  claim 36 , wherein the EphB6 function is further defined as T-cell EphB6 function of a human T-cell.  
   
   
       40 . A method of treating a disorder of T-cell proliferation, an autoimmune disorder, a cell-associated autoimmune disorder, an allergic disorder in an animal, or a host verses transplant rejection, comprising modulating T-cell expression of EphB receptor.  
   
   
       41 . The method according to  claim 40 , wherein T-cell expression of EphB receptor is modulated by ephrin-B1, ephrin -B2, an antibody or antibody fragment capable of binding EphB6, or an antisense molecule to EphB6.  
   
   
       42 . The method according to  claim 40 , wherein the cell-associated autoimmune disorder is multiple sclerosis, lupus, arthritis, thyroiditis, diabetes, psoriasis, Crohn's disease or colitis.  
   
   
       43 . The method according to  claim 40 , wherein the allergic disorder is asthma, hyper-IgE syndrome, eosinophilic syndrome, or a T cell-dependent graft-verses-host disease.  
   
   
       44 . The method according to  claim 40 , wherein the EphB6 function is further defined as EphB6 function of a human T-cell.  
   
   
       45 . A method of promoting an anti-viral immune response in an animal, comprising modulating T-cell expression of EphB receptor thereby promoting the antiviral response in the animal.  
   
   
       46 . The method according to  claim 45 , wherein modulating T-cell expression of EphB receptor comprises administering ephrin-B1, ephrin- B2, an antibody or antibody fragment capable of binding EphB6, or an antisense molecule to EphB6.  
   
   
       47 . The method according to  claim 45  wherein the substance is soluble stimulatory or inhibitory ephrin and/or a soluble EphB6 receptor.  
   
   
       48 . A method for identifying a substance which is capable of binding to a purified and isolated EphB6 protein, comprising reacting the protein with at least one substance which potentially can bind with the protein under conditions which permit the formation of complexes between the substance and the protein, and assaying for complexes, for free substance, for non-complexed protein, or for activation of the protein.  
   
   
       49 . A method for assaying a medium for the presence of an agonist or antagonist of the interaction of a purified and isolated a EphB6 protein and a substance which binds to the protein which comprises reacting the protein with a substance which is capable of binding to the protein and a suspected agonist or antagonist substance under conditions which permit the formation of complexes between the substance and the protein, and assaying for complexes, for free substance, for non-complexed protein, or for activation of the protein.