Antigen presenting system and methods for activation of T-cells

Abstract

The present invention relates to synthetic antigen-presenting matrices, their methods of making and their methods of use. One such matrix is cells that have been transfected to produce MHC antigen-presenting molecules and assisting molecules such as co-stimulatory molecules. The matrices can be used to activate CD8 + T-cells to produce cytokines and become cytotoxic.

1 . A synthetic antigen-presenting matrix comprising: 
 a) a support;    b) extracellular portion of MHC molecules capable of binding to a selected peptide and being operably linked to the support; and    c) an assisting molecule operably linked to the support such that the extracellular portion of the MHC and assisting molecules are present in sufficient numbers to activate a population of T-cell lymphocytes against the peptide when the peptide is bound to the extracellular portion of the MHC molecule;    and wherein the peptide is bound to the extracellular portion of the MHC molecule.    
     
     
         2 . A method of treating a tumor in a patient comprising: 
 a) identifying a tumor specific antigen;    b) collecting CD8 +  T-cells from the patient;    c) contacting the CD8 +  T-cells with the matrix of  claim 1  in vitro in a sufficient amount and for a sufficient time to generate cytotoxic CD8 +  T-cells; and    d) returning the cytotoxic CD8 +  T-cells to the patient.    
     
     
         3 . The method of  claim 2  wherein the antigen is a self antigen of the patient.  
     
     
         4 . The method of  claim 3  wherein the assisting molecule is a combination of a costimulatory molecule selected from the group consisting of B7.1 and B7.2, and an adhesion molecule selected from the group consisting of ICAM-1, ICAM-2 and ICAM-3.  
     
     
         5 . The method of  claim 4  wherein the assisting molecule is B7.1 and the adhesion molecule is ICAM-1.  
     
     
         6 . A synthetic antigen-presenting matrix comprising: 
 a) a support;    b) extracellular portion of MHC molecules capable of binding to a selected peptide and being operably linked to the support;    c) B-7.1 or B-7.2 molecules or a combination thereof operably linked to the support; and    d) ICAM-1 molecules operably linked to the support such that the molecules are present in sufficient amount to activate a population of T-cell lymphocytes against the peptide when the peptide is bound to the extracellular portion of the MHC molecule.