Method for identifying ligands, inhibitors or promoters of CXC chemokine receptor 3

A method of detecting or identifying an agent which binds a mammalian CXCR3 protein or a ligand binding variant thereof comprising:

• a) combining an agent to be tested and a host cell expressing recombinant mammalian CXCR3 protein or a ligand binding variant thereof under conditions suitable for binding of ligand to said mammalian CXCR3 protein or ligand binding variant;
• and
• b) detecting or measuring the formation of a complex between said agent and said mammalian CXCR3 protein or ligand binding variant,
• wherein said mammalian CXCR3 protein or ligand binding variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and shares at least 90% amino acid sequence identity with SEQ D NO:2.

A method of detecting or identifying an inhibitor of ligand binding to a mammalian CXCR3 protein or a ligand binding variant thereof comprising:

• a) combining an agent to be tested, a ligand of said mammalian CXCR3 protein and a composition comprising isolated and/or recombinant mammalian CXCR3 protein or ligand binding variant thereof under conditions suitable for binding of ligand to said mammalian CXCR3 protein or ligand binding variant;
• and
• b) detecting or measuring the formation of a complex between said mammalian CXCR3 protein or ligand binding variant and said ligand,
• wherein inhibition of complex formation by the agent is indicative that the agent is an inhibitor, and
• said mammalian CXCR3 protein or ligand binding variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and shares at least 90% amino acid sequence identity with SEQ ID NO:2.

A method of detecting or identifying an inhibitor of ligand binding to a mammalian CXCR3 protein or ligand binding variant thereof comprising:

• a) combining an agent to be tested, a ligand of said mammalian CXCR3 protein and a host cell expressing a recombinant mammalian CXCR3 protein or ligand binding variant thereof under conditions suitable for binding of ligand to said mammalian CXCR3 protein or ligand binding variant;
• and
• b) detecting or measuring the formation of a complex between said mammalian CXCR3 protein or ligand binding variant and said ligand,
• wherein inhibition of complex formation by the agent is indicative that the agent is an inhibitor, and
• said mammalian CXCR3 protein or ligand binding variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and shares at least 90% amino acid sequence identity with SEQ ID NO:2.

A method of detecting or identifying an inhibitor of a mammalian CXCR3 protein or functional variant thereof comprising combining an agent to be tested,

• (a) a host cell expressing a recombinant mammalian CXCR3 protein or functional variant thereof, and
• (b) a ligand or promoter of said mammalian CXCR3 protein or functional variant, under conditions suitable for detecting a ligand- or promoter-induced response, and assessing the ability of the test agent to inhibit said response,
• wherein inhibition of a ligand- or promoter-induced response by the agent is indicative that the agent is an inhibitor, and
• said mammalian CXCR3 protein or functional variant selectively binds at least one chemokine selected from the group consisting of IF-10 and Mig, and shares at least 90% amino acid sequence identity with SEQ ID NO:2.

A method of detecting or identifying an inhibitor of ligand biding to a mammalian CXCR3 protein or a ligand binding variant thereof comprising:

• a) combining an agent to be tested, a ligand of said mammalian CXCR3 protein and a composition comprising isolated an/or recombinant mammalian CXCR3 protein or a ligand binding variant thereof under conditions suitable for binding of ligand to said mammalian CXCR3 protein or ligand binding variant;
• and
• b) detecting or measuring the formation of a complex between said mammalian CXCR3 protein or ligand binding variant and said ligand,
• wherein inhibition of complex formation by the agent is indicative that the agent is an inhibitor, and
• said mammalian CXCR3 protein or ligand binding variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and is encoded by a nucleic acid sharing at least 90% nucleotide sequence similarity with the coding region of the sequence illustrated in SEQ ID NO:1.

A method of detecting or identifying an inhibitor of a mammalian CXCR3 protein or functional variant thereof comprising combining an agent to be tested,

• (a) a host cell expressing a recombinant mammalian CXCR3 protein or functional variant thereof, and
• (b) a ligand or promoter of said mammalian CXCR3 protein or functional variant, under conditions suitable for detecting a ligand- or promoter-induced responses, and assessing the ability of the test agent to inhibit said response,
• wherein inhibition of a ligand- or promoter-induced response by the agent is indicative that the agent is an inhibitor, and
• said mammalian CXCR3 protein or functional variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and is encoded by a nucleic acid sharing at least 90% nucleotide sequence similarity with the coding region of the sequence illustrated in SEQ ID NO:1.

A method of detecting or identifying an inhibitor of ligand binding to a human CXCR3 protein comprising:

• a) combining an agent to be tested, a ligand of said CXCR3 protein and a composition comprising recombinant human CXCR3 protein under conditions suitable for binding of ligand to said human CXCR3 protein;
• and
• b) detecting or measuring the formation of a complex between said human CXCR3 protein and said ligand,
• wherein inhibition of complex formation by the agent is indicative that the agent is an inhibitor, and
• said human CXCR3 protein selectively binds at least one chemokine selected from the group consisting of human IP-10 or human Mig and comprises the extracellular N-terminal segment of the protein shown in FIG. 2 (SEQ ID NO:2).

A method of detecting or identifying an inhibitor of ligand binding to a human CXCR3 protein comprising:

• a) combining an agent to be tested, a ligand of said human CXCR3 protein and a host cell expressing a recombinant human CXCR3 protein under conditions suitable for binding of ligand to said human CXCR3 protein;
• and
• b) detecting or measuring the formation of a complex between said protein and said ligand,
• wherein inhibition of complex formation by the agent is indicative that the agent is an inhibitor, and
• said human CXCR3 protein selectively binds at least one chemokine selected from the group consisting of human IP-10 or human Mig and comprises the extracellular N-terminal segment of the protein shown in FIG. 2 (SEQ ID NO:2).

A method of detecting or identifying an agent which binds a mammalian CXCR3 protein or ligand binding variant thereof, comprising combining an agent to be tested and a composition comprising an isolated and/or recombinant mammalian CXCR3 protein or ligand big variant thereof under conditions suitable for binding of ligand to said ian CXCR3 protein or ligand binding variant, and detecting or measuring the formation of a complex between said agent and said mammalian CXCR3 protein or ligand binding variant,

• wherein said mammalian CXCR3 protein or ligand binding variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and is encoded by a nucleic acid that hybridizes, under high stringency wash conditions of 2×SSC, 0.1% SDS at room temperature for ten minutes followed by two washes in 1×SSC, 0.1% SDS at 65° C. for thirty minutes and a final wash in 0.5×SSC, 0.1% SDS at 65° C. for ten minutes, to a nucleic acid selected from the group consisting of:
• a) the complement of SEQ ID NO:1;
• and
• b) the complement of a portion of SEQ ID NO:1 comprising the open reading frame.

A method of detecting or identifying an inhibitor of ligand binding to a mammalian CXCR3 protein or a ligand binding variant thereof comprising:

• a) combining an agent to be tested, a ligand of said mammalian CXCR3 protein and a composition comprising isolated and/or recombinant an CXCR3 protein or a ligand binding variant thereof under conditions suitable for binding of ligand to said mammalian CXCR3 protein or ligand binding variant;
• and
• b) detecting or measuring the formation of a complex between said mammalian CXCR3 protein or ligand binding variant and said ligand,
• wherein inhibition of complex formation by the agent is indicative that the agent is an inhibitor, and
• said ma mammalian CXCR3 protein or ligand binding variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and is encoded by a nucleic acid that hybridizes, under high stringency wash conditions of 2×SSC, 0.1% SOS at room temperature for ten minutes followed by two washes in 1×SSC, 0.1% SDS at 65° C. for thirty minutes and a final wash in 0.5×SSC, 0.1% SDS at 65° C. for ten minutes, to a nucleic acid selected from the group consisting of:
• i) the complement of SEQ ID NO:1;
• and
• ii) the complement of a portion of SEQ ID NO:1 comprising the open reading frame.

A method of detecting or identifying an inhibitor of a mammalian CXCR3 protein or functional variant thereof comprising combining an agent to be tested,

• (a) a host cell expressing a recombinant mammalian CXCR3 protein or functional variant thereof, and
• (b) a ligand or promoter of said mammalian CXCR3 protein, under conditions suitable for detecting a ligand- or promoter-induced response, and assessing the ability of the test agent to inhibit said response,
• wherein inhibition of a ligand- or promoter-induced response by the agent is indicative that the agent is an inhibitor, and
• said mammalian CXCR3 protein or functional variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and is encoded by a nucleic acid that hybridizes, under high stringency wash conditions of 2×SSC, 0.1% SDS at room temperature for ten minutes followed by two washes in 1×SSC, 0.1% SDS at 65° C. for thirty minutes and a final wash in 0.5×SSC, 0.1% SDS at 65° C. for ten minutes, to a nucleic acid selected from the group consisting of:
• i) the complement of SEQ D NO:1;
• and
• ii) the complement of a portion of SEQ ID NO:1 comprising the open reading frame.

A method of detecting or identifying a promoter of a mammalian CXCR3 protein or functional variant thereof comprising combining an agent to be tested and a host cell expressing a recombinant mammalian CXCR3 protein or functional variant thereof under conditions suitable for detecting a receptor-mediated response, and detecting or measuring said response,

• wherein induction or stimulation of said response by the agent is indicative that the agent is a promoter, and
• said mammalian CXCR3 protein or functional variant selectively binds at least one chemokine selected from the group consisting of IP-10 and Mig, and is encoded by a nucleic acid that hybridizes, under high stringency wash conditions of 2×SSC, 0.1% SDS at room temperature for ten minutes followed by two washes in 1×SSC, 0.1% SDS at 65° C. for thirty minutes and a final wash in 0.5×SSC, 0.1% SDS at 65° C. for ten minutes, to a nucleic acid selected from the group consisting of:
• i) the complement of SEQ ID NO:1;
• and
• ii) the complement of a portion of SEQ ID NO:1 comprising the open reading frame.