Method for modularting activity of t lymphocytes

Abstract

The invention relates to methods and compositions which modulate T lymphocyte activity. It has been found that two, T lymphocyte receptors, especially TCR and CD8, are present at a distance from each other on T lymphocyte surfaces. Via use of modulators which change the distance between these receptors, the activity of the T lymphocyte is modulated.

1 . A method for modulating activity of a T lymphocyte, comprising contacting said T lymphocyte with a substance that changes distance between a T lymphocyte receptor and a T lymphocyte co-receptor to a point sufficient to modulate activity of said T lymphocyte. 
     
     
         2 . The method of  claim 1 , wherein said T lymphocyte co-receptor is a CD8 molecule. 
     
     
         3 . The method of  claim 1 , wherein said T lymphocyte receptor is a T cell receptor molecule. 
     
     
         4 . The method of  claim 1 , wherein said substance reduces distance between a T lymphocyte receptor and a T lymphocyte co-receptor and increases activity of said T lymphocyte. 
     
     
         5 . The method of  claim 2 , wherein said substance is a zinc chelator. 
     
     
         6 . The method of  claim 4 , wherein said zinc chelator is o-phenantholin. 
     
     
         7 . The method of  claim 4 , wherein said substance is an N-glycosylation pathway inhibitor. 
     
     
         8 . The method of  claim 7 , wherein said inhibitor is a β1-6-N-acetyl glucosaminyl transferase inhibitor. 
     
     
         9 . The method of  claim 7 , wherein said inhibitor is swainsonin. 
     
     
         10 . The method of  claim 4 , wherein said substance is a galectin-3 ligand. 
     
     
         11 . The method of  claim 10 , wherein said galectin-3 ligand is lactose. 
     
     
         12 . The method of  claim 10 , wherein said galectin-3 ligand is an oligosaccharide which comprises an N-acetyl-lactosamine motif. 
     
     
         13 . The method of  claim 12 , wherein said oligosaccharide is N-acetyl-lactosamine. 
     
     
         14 . The method of  claim 1 , wherein said T lymphocyte is specific for a complex of an MHC molecule and a cancer associated peptide. 
     
     
         15 . The method of  claim 1 , wherein said activity is target cell lysis. 
     
     
         16 . A method for determining if a substance modulates activity a T lymphocyte, comprising determining distance between a TCR molecule and a CD8 molecule on said T lymphocyte prior to contact with said substance, followed by determination of said distance after said contact, a difference there between being indicative of a substance which modulates activity of said T lymphocyte. 
     
     
         17 . The method of  claim 16 , comprising FRET analysis. 
     
     
         18 . Composition useful in modulating T cell production comprising at least one peptide which binds to an MHC molecule and a substance which changes distance between a T lymphocyte receptor and co-receptor to a point sufficient to modulate T lymphocyte activity. 
     
     
         19 . Composition useful in modulating T cell production comprising at least one vaccine material and a substance which changes distance between a T lymphocyte receptor and co-receptor to a point sufficient to modulate T lymphocyte activity. 
     
     
         20 . The composition of  claim 19 , comprising a full length, tumor rejection antigen precursor protein. 
     
     
         21 . The composition of  claim 19 , comprising a recombinant virus which expresses all or a part of a tumor rejection antigen precursor. 
     
     
         22 . The composition of  claim 19 , further comprising an adjuvant.