ILT3 polypeptides and uses thereof
This invention provides a first polypeptide comprising all or a portion of the extracellular domain of ILT3, wherein the polypeptide is water-soluble and does not comprise the Fc portion of an immunoglobulin. This invention also provides a second polypeptide comprising (i) all or a portion of the extracellular domain of ILT3 operable affixed to (ii) the Fc portion of an immunoglobulin, wherein the Fc portion of the immunoglobulin comprises a function-enhancing mutation, and wherein the polypeptide is water-soluble. This invention further provides a third polypeptide comprising (i) all or a portion of the extracellular domain of ILT3 operable affixed to (ii) a transmembrane domain. This invention further provides related nucleic acids, expression vectors, host vector systems, compositions, and articles of manufacture and therapeutic and prophylactic methods using the polypeptides of the invention.
1. A method comprising:
(i) identifying a subject that has an autoimmune disorder selected from the group consisting of: multiple sclerosis, lupus vulgaris, thyroiditis, Addison's Disease, antiphospholipid syndrome, dermatitis, allergic encephalomyelitis, Goodpasture's Syndrome, Graves' Disease, Myasthenia Gravis, Neuritis, Ophthalmia, Bullous Pemphigoid, Pemphigus, Polyendocrinepathies, Reiter's Disease, Stiff-Man Syndrome, Autoimmune Pulmonary Inflammation, Guillain-Barre Syndrome, and autoimmune inflammatory eye disease, and
(ii) administering to the subject an immunosuppressive amount of a soluble polypeptide comprising the extracellular domain of human ILT3.
2. The method of claim 1 , wherein the polypeptide is administered to the subject during a flare-up of the autoimmune disorder.
3. The method of claim 1 , wherein the subject is a mammal, preferably a human.
4. The method of claim 1 , wherein the soluble polypeptide is operably affixed to an Fc portion of an immunoglobulin.
5. The method of claim 4 , wherein the Fc portion comprises a function-enhancing mutation that inhibits binding of the Fc portion to an Fc receptor.
6. The method of claim 5 , wherein the function-enhancing mutation in the Fc portion is an Asn >Gln point mutation at the N-linked glycosylation site of human IgG1.
7. The method of claim 4 , wherein the Fc portion of the immunoglobulin is an Fc portion of human IgG1.
8. A method comprising:
(i) identifying a subject that has an autoimmune disorder selected from the group consisting of:
multiple sclerosis, lupus vulgaris, thyroiditis, Addison's Disease, antiphospholipid syndrome, dermatitis, allergic encephalomyelitis, Goodpasture's Syndrome, Graves' Disease, Myasthenia Gravis, Neuritis, Ophthalmia, Bullous Pemphigoid, Pemphigus, Polyendocrinepathies, Reiter's Disease, Stiff-Man Syndrome, Autoimmune Pulmonary Inflammation, Guillain-Barre Syndrome, and autoimmune inflammatory eye disease, and
(ii) administering a soluble polypeptide comprising the extracellular domain of human ILT3 to the subject in an amount sufficient to induce anergy in CD3+T cells under conditions permitting priming of the CD3+T cells to occur, thereby inducing CD8+T cells to differentiate into regulatory CD8+T cells.
9. The method of claim 8 , wherein the conditions permitting priming to occur comprise contacting the CD3+T cells with allogeneic antigen presenting cells or with autologous antigen presenting cells pulsed with a desired antigen.
10. The method of claim 9 , wherein the allogeneic antigen presenting cells are irradiated KG1 cells.
11. The method of claim 9 , wherein differentiation of the CD8+T cells into a regulatory CD8+T cells is determined by detecting expression of a regulatory T cell marker, or assaying ability of the CD8+T cells to inhibit a mixed lymphocyte response to an allogeneic antigen presenting cell or to an autologous antigen presenting cell pulsed with a desired antigen.
12. A method comprising:
(i) identifying a subject that has graft vs. host disease, and
(ii) administering to the subject an immunosuppressive amount of a soluble polypeptide comprising the extracellular domain of human ILT3.
13. A method comprising:
(i) identifying a subject that has had a tissue or cell transplant, and
(ii)administering to the subject an immunosuppressive amount of a soluble polypeptide comprising the extracellular domain of human ILT3.
14. The method of claim 13 , wherein the tissue is vascular tissue.
15. The method of claim 13 , wherein the transplanted cells are selected from the group comprising stem cells, pancreatic islet cells, epithelial cells, endothelial cells, and liver cells.
16. The method of claim 13 , wherein the polypeptide is administered to the subject either concurrently with, or after, a peripheral mononuclear blood cell transplantation.