Methods for modulating an immune response by modulating the interaction between CTLA4 and PP2A
AssigneeGenetics Institute, Inc.
InventorsJoaquin Madrenas, Mary Collins, Beatriz Carreno, Vijay Kuchroo
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Abstract
The present invention provides methods for modulating an immune response comprising contacting a cell with an agent that modulates the interaction between CTLA4 and PP2AA via modulating the lysine rich motif of CTLA4. The invention further provides methods for treating a subject having a disorder that would benefit from down regulation of an immune response comprising administering an agent that modulates the interaction between CTLA4 and PP2AA via modulating the lysine rich motif of CTLA4. The invention also provides methods for identifying compounds capable of modulating the interaction of CTLA4 and PP2AA.
Claims54
A method for modulating an immune response comprising contacting a cell expressing at least one first molecule having a CTLA4 lysine rich motif and at least one second molecule having a PP2AA CTLA4-interacting domain with an agent that modulates the interaction between the first molecule and the second molecule to thereby modulate the immune response.
A method for treating a subject having a condition that would benefit from downregulation of an immune response comprising administering an agent that inhibits the interaction between interaction between a first molecule having a CTLA4 lysine rich motif and a second molecule having a PP2AA CTLA4-interacting domain in at least one T cell of the subject such that a condition that would benefit from downregulation of an immune response is treated.
A method for treating a subject having a condition that would benefit from downregulation of an immune response, comprising:
- a) contacting T cells expressing at least one first molecule having a CTLA4 lysine rich motif and at least one second molecule having a PP2AA CTLA4-interacting domain from the subject with an agent that modulates the interaction between the first molecule and the second molecule, and
- b) administering the T cells to the subject, such that a condition that would benefit from downregulation of an immune response is treated.
A method for identifying a compound which modulates the interaction of CTLA4 and PP2AA comprising contacting a cell comprising at least one first molecule having a CTLA4 cytoplasmic domain containing a lysine rich motif and at least one second molecule having a PP2AA CTLA4-interacting domain with a test compound and determining the ability of the test compound to modulate the interaction of the first molecule and the second molecule.
A method for identifying a compound which modulates the interaction of a CTLA4 molecule and a PP2AA molecule comprising:
- a) contacting, in the presence of the compound, a first molecule comprising at least a portion of the CTLA4 molecule and a second molecule comprising at least a portion of the PP2AA molecule under conditions which allow binding of the first molecule and the second molecule to form a complex;
- and
- b) detecting the formation of a complex of the first molecule and the second molecule in which the ability of the compound to modulate interaction between the first molecule and the second molecule is indicated by a change in complex formation as compared to the amount of complex formed in the absence of the compound.
A method for identifying a compound which modulates the interaction of a molecule comprising at least one CTLA4 lysine rich motif and a PP2AA molecule comprising a PP2AA CTLA4-interacting domain comprising:
- a) contacting the molecule comprising at least one CTLA4 lysine rich motif with the compound;
- and
- b) detecting binding of the compound to the CTLA4 lysine rich motif of the molecule, to thereby identify a compound which modulates the interaction of a molecule comprising at least one CTLA4 lysine rich motif and a PP2AA molecule.
Dependencies are inferred from the claim text.