COMPOSITIONS AND METHODS OF MONOCLONAL AND POLYCLONAL ANTIBODIES SPECIFIC FOR T CELL SUBPOPULATIONS
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 . (canceled)
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 phytohemagglutinin (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 phytohemagglutinin (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 - 22 . (canceled)