Compositions and methods of monoclonal and polyclonal antibodies specific for t cell subpopulations

Abstract

The invention provides compounds and methods for the ex vivo or in vivo expansion of NK T cells, CD1d-reactive T cells, and JαQ + T cells, and the modulation of their activities. These compounds and methods have diagnostic and therapeutic applications.

1 . A purified antibody, or fragment or derivative thereof, that preferentially binds a T cell antigen receptor (TCR), wherein said antibody:
 (a) preferentially binds a CDR3-loop or an α-β junction of said TCR; or   (b) preferentially binds or modulates the expansion or activation of at least one T cell subpopulation selected from the group of NK T cells, CD1d-reactive T cells, and JαQ +  T cells.   
     
     
         2 . The purified antibody, fragment, or derivative of  claim 1  that preferentially binds and preferentially expands an invariant T cell. 
     
     
         3 . A method of treating an autoimmune disease, viral infection, bacterial infection, parasitic infection, infection by a eukaryotic pathogen, graft versus host disease, graft rejection, immunodeficiency disease, spontaneous abortion, or pregnancy in a mammal, said method comprising administering to said mammal an antibody, fragment, or derivative of  claim 1 . 
     
     
         4 . A method of treating an allergy, asthma, or an inflammatory condition in a mammal, said method comprising administering to said mammal an antibody, fragment, or derivative of  claim 1 , wherein said antibody, fragment, or derivative inhibits expansion or activation of at least one of said T cell subpopulations. 
     
     
         5 . The method of  claim 4 , wherein said antibody, fragment, or derivative is covalently linked to a toxin or a radiolabel. 
     
     
         6 . A method of treating cancer or type I diabetes in a mammal, said method comprising administering to said mammal an antibody, fragment, or derivative of  claim 1 , wherein said antibody expands or activates at least one of said T cell subpopulations. 
     
     
         7 . A method of inhibiting T cell pathogenesis in a mammal, said method comprising administering to said mammal an antibody, fragment, or derivative of  claim 1 . 
     
     
         8 . A method of producing a purified population of invariant T cells from a sample containing T cells, said method comprising:
 (a) contacting said population with an antibody, fragment, or derivative of  claim 1 ; and   (b) separating the cells bound to said antibody, fragment, or derivative from said population.   
     
     
         9 . A purified T cell subpopulation produced by the method of  claim 8 . 
     
     
         10 . A method of expanding a population of invariant T cells purified by the method of  claim 8 , said method comprising:
 (a) contacting said cells with an antibody, antigen, cytokine, or mitogen capable of expanding said population; and   (b) optionally administering said expanded population to a mammal.   
     
     
         11 . The method of  claim 10 , wherein:
 (a) said antibody capable of expanding said population is selected from the ground consisting of an antibody of  claim 1 , anti-Vα24, and anti-CD30; or a fragment or derivative thereof;   (b) said antigen is a glycosyl-phosphatidylinositol antigen from an infectious pathogen, an antigen from a cancerous cell, a self-lipid, or α-galactosylceramide;   (c) said cytokine is IL-2, IL-4, IL-7, IL-10, IL-12, IL-13, IL-15, IL-18, IFN-α/β, IFN-γ, or GM-CSF; or   (d) said mitogen is phytohaemagglutinin (PHA) or PMA/ionomycin.   
     
     
         12 . A method of producing an expanded population of invariant T cells, said method comprising:
 (a) contacting a population of T cells containing invariant T cells with an antibody, antigen, cytokine, or mitogen capable of expanding invariant T cells in said population;   (b) contacting said population of step (a) with an antibody of  claim 1 ;   (c) separating said cells that bind the antibody of step (b) from said population, thereby producing an expanded population of invariant T cells; and   (d) optionally administering said expanded population to a subject.   
     
     
         13 . The method of  claim 12 , wherein:
 (a) said antibody capable of expanding said population is selected from the ground consisting of an antibody of  claim 1 , anti-Vα24, and anti-CD3; or a fragment or derivative thereof;   (b) said antigen is a glycosyl-phosphatidylinositol antigen from an infectious pathogen, an antigen from a cancerous cell, a self-lipid, or α-galactosylceramide;   (c) said cytokine is IL-2, IL-4, IL-7, IL-10, IL-12, IL-13, IL-15, IL-18, IFN-α/β, IFN-γ, or GM-CSF; or   (d) said mitogen is phytohaemagglutinin (PHA) or PMA/ionomycin.   
     
     
         14 . A method of expanding a subpopulation of T cells, said method comprising contacting a sample comprising said T cells with an antibody, fragment, or derivative of  claim 1 , wherein said contacting occurs under conditions sufficient to produce an increase in the number of said T cells. 
     
     
         15 . The method of  claim 14 , wherein said method is performed in vivo. 
     
     
         16 . The method of  claim 14 , further comprising contacting said sample with an antigen and antigen presenting cells under conditions that allow said contacting to increase the number of said T cells. 
     
     
         17 . The method of  claim 16 , wherein said antigen is a lipid or glycosyl-phosphatidylinositol antigen from an infectious pathogen, an antigen from a cancerous cell, or a self-lipid. 
     
     
         18 . The method of  claim 14 , further comprising contacting said sample with one or more cytokines. 
     
     
         19 . A method of increasing the size of a subpopulation of T cells in a mammal, said method comprising:
 (a) obtaining a sample comprising said T cells from said mammal;   (b) contacting said T cells with an antibody, fragment, or derivative of  claim 1  under conditions sufficient to increase the size of said subpopulation; and   (c) administering said contacted T cells to said mammal.   
     
     
         20 . The method of  claim 19 , further comprising isolating said T cells prior to said contacting step or after said contacting step. 
     
     
         21 . The method of  claim 10 ,  12 , or  19 , wherein said method is used in the treatment of cancer, autoimmune disease, viral infection, bacterial infection, parasitic infection, infection by a eukaryotic pathogen, graft versus host disease, graft rejection, immunodeficiency disease, spontaneous abortion, or pregnancy in a mammal. 
     
     
         22 . The method of  claim 21 , wherein said autoimmune disease is type I diabetes.