Reivindicaciones
Claims : 1. A method of targeting a peptide antigen to an antigen presenting cell, comprising contacting the antigen presenting cell with a composition comprising the antigen, wherein the antigen is associated with a binding agent having affinity for CLEC9a, and wherein the antigen presenting cell expresses CLEC9a. 2. A method according to claim 1 wherein the antigen presenting cell is a dendritic cell. 3. A method according to claim 2 wherein the dendritic cell is capable of cross-presenting extracellular antigen via MHC class I molecules. 4. A method according to any one of claims 1 to 3 performed in vitro or in vivo . 5. A method of stimulating an immune response against a peptide antigen in a subject, comprising administering to the subject a composition comprising the antigen, wherein the antigen is associated with a binding agent having affinity for CLEC9a. 6. A method according to claim 5 comprising more than one administration of said composition. 7. A composition comprising a peptide antigen, wherein the antigen is associated with a binding agent having affinity for CLEC9a. 8. A composition according to claim 7 wherein said composition comprises said antigen and said binding agent in combination with a pharmaceutically acceptable carrier. 9. A composition according to claim 7 or claim 8 formulated, for intravenous, intramuscular, intraperitoneal, nasal, subcutaneous or intradermal administration. 10. A composition according to any one of claims 7 to 9, for use in a method of medical treatment. 11. A composition according to any one of claims 7 to 10, for use in stimulating an immune response against the antigen. 12. Use of a composition according to any one of claims 7 to 11 in the preparation of a medicament for stimulating an immune response against the antigen. 13. A method, composition or use according to any one of claims 1 to 12 wherein the immune response to be stimulated is a CTL response or a Treg response . 14. A method, composition or use according to any one of claims 1 to 13 wherein the composition is administered, or is formulated for administration with, an adjuvant. 15. A method, composition or use according to claim 14 wherein the adjuvant is retinoic acid, a CD40 agonist or a TLR agonist, or another immunostimulatory agent. 16. A method, composition or use according to any one of claims 1 to 15 wherein the antigen is covalently coupled to the binding agent . 17. A method, composition or use according to claim 17 wherein the antigen and binding agent are part of the same peptide chain. 18. A method, composition or use according to any one of claims 1 to 17 wherein the binding agent comprises an antibody binding site specific for CLEC9a. 19. A method, composition or use according to claim 18 wherein the binding agent is an antibody or functional fragment thereof . 20. A method, composition or use according to any one of claims 1 to 19 wherein the binding agent is an agonist of CLEC9a. 21. A method, composition or use according to any one of claims 1 to 20 wherein the binding agent has at least two binding sites for CLEC9a. 22. A method, composition or use according to any one of claims 1 to 21 wherein the antigen is or comprises a peptide from a protein expressed by a pathogen or parasite, or a protein from a cancer cell. 23. A method, composition or use according to claim 22 wherein the antigen is a viral protein or a tumour-specific antigen. 24. A method, composition or use according to claim 13 wherein the response is a Treg response and wherein the antigen is one against which it is desirable to inhibit or suppress an undesirable immune response. 25. A method of inhibiting an immune response in a subject comprising administering a CLEC9a antagonist to the subject. 26. A method according to claim 25 wherein the antagonist is a binding agent having affinity for CLEC9a or a nucleic acid encoding a binding agent having affinity for CLEC9a. 27. A method according to claim 26 wherein the binding agent is capable of directly or indirectly inhibiting function of a cell to which it is bound. 28. A method according to claim 27 wherein the binding agent is directly or indirectly capable of killing the cell. 29. A method according to claim 27 or claim 28 wherein the binding agent is capable of recruiting components of the subject's immune system, thus stimulating an immune attack on the cell. 30. A method according to any one of claims 26 to 29 wherein the binding agent comprises an antibody Fc region 31. A method according to claim 28 wherein the binding agent comprises a toxin molecule capable of killing the cell. 32. A method according to claim 28 wherein the binding agent comprises an enzyme capable of activating a prodrug in the vicinity of the cell . 33. A method according to claim 32 wherein the enzyme converts a non-toxic molecule into a toxic molecule. 34. A method according to any one of claims 26 to 33 wherein the binding agent comprises an antibody binding site specific for CLEC9a. 35. A method according to any one of claims 26 to 34 wherein the binding agent has only one binding site specific for CLEC9a. 36. A method according to claim 25 wherein the CLEC9a antagonist is capable of inhibiting CLEC9a binding to its ligand. 37. A method according to claim 36 wherein the CLEC9a antagonist is a soluble molecule comprising the extracellular domain of CLEC9a or a fragment thereof capable of binding to CLEC9a ligand. 38. A method according to any one of claims 25 to 37 wherein the subject to whom the antagonist is administered is suffering from an inflammatory or autoimmune condition, especially a condition characterised by undesirable CTL activity. 39. A method according to claim 38 wherein the condition is selected from: - autoimmune diseases, including rheumatoid arthritis and other types of chronic or acute arthritis or arthropathies with an immune component, systemic lupus erythematosus, scleroderma, Sjogren syndrome, autoimmune (particularly Type I) diabetes, thyroiditis, and other organ-specific immune diseases, including psoriasis; - neurologic diseases, including multiple sclerosis, myasthenia gravis, and other neurologic immune-mediated diseases ; - gastrointestinal diseases, including Crohn's disease, colitis, celiac disease and hepatitis,- - cardiovascular diseases, including atherosclerosis, cardiomyopathy, rheumatic fever, endocarditis, vasculitis, and other immune-mediated cardiovascular diseases; - immune-mediated respiratory diseases, including emphysema, respiratory airways infections, and other immune-mediated respiratory diseases; - allergic processes and hypersensitivity reactions (type I, II, III, and IV) , including asthma, rhinitis, and other immune-mediated hypersensitivity reactions; - transplant or graft rejection and graft versus host disease, as occurs during or subsequent to, for example, organ transplant, tissue graft, blood transfusion, bone marrow transplant ; - immunopathological responses to infectious agents, including septic shock syndromes; - degenerative processes, such as neurodegenerative processes, that implicate immune competent cells such as microglia. 40. A CLEC9a antagonist, or a binding agent having affinity for CLEC9a, for use in a method of medical treatment. 41. A CLEC9a antagonist, or a binding agent having affinity for CLEC9a, for use in the inhibition of an immune response. 42. Use of a CLEC9a antagonist, or a binding agent having affinity for CLEC9a in the preparation of a medicament for the inhibition of an immune response. 43. A binding agent or use according to any one of claims 40 to 42 which comprises an antibody binding site specific for CLEC9a. 44. A binding agent or use according to any one of claims 40 to 43 wherein the binding agent is capable of directly or indirectly inhibiting antigen presentation by a cell to which it is bound. 45. A binding agent or use according to claim 44 wherein the binding agent is directly or indirectly capable of killing the cell. 46. A binding agent or use according to claim 44 or claim 45 wherein the binding agent is capable of recruiting components of the subject's immune system, thus stimulating an immune attack on the cell . 47. A binding agent or use according to claim 46 wherein the binding agent comprises an antibody Fc region 48. A binding agent or use according to claim 45 wherein the binding agent comprises a toxin molecule capable of killing the cell. 49. A binding agent or use according to claim 45 wherein the binding agent comprises an enzyme capable of activating a prodrug in<'>the vicinity of the cell. 50. A binding agent or use according to claim 49 wherein the enzyme converts a non-toxic molecule into a toxic molecule. 51. A CLEC9a antagonist or use according to any one of claims 40 to 42 wherein the CLEC9a antagonist is capable of inhibiting CLEC9a binding to its ligand. 52. A CLEC9a antagonist or use according to claim 51 wherein the CLEC9a antagonist is a soluble molecule comprising the extracellular domain of CLEC9a or a fragment thereof capable of binding to CLEC9a ligand. 53. A method of stimulating an immune response in a subject comprising administering a CLEC9a agonist to the subject. 54. A method according to claim 53 wherein the agonist is a binding agent having affinity for CLEC9a. 55. A method according to claim 54 wherein the binding agent comprises an antibody binding site specific for CLEC9a. 56. A method according to claim 54 or claim 55 wherein the binding agent comprises more than two binding sites specific for CLEC9a. 57. A method of detecting a cell in a sample, comprising contacting the sample with a binding agent having affinity for CLEC9a and determining binding of the binding agent to one or more cells. 58. A method of isolating a cell from a sample, comprising contacting the sample with a binding agent having affinity for CLEC9a and isolating one or more cells to which the binding agent is bound. 59. A method according to claim 57 or claim 58 wherein the binding agent is immobilised on a solid support. 60. A method according to any one of claims 57 to 59 wherein the antigen presenting cell is a dendritic cell . 61. A method according to claim 60 wherein the dendritic cell is capable of cross-presenting extracellular antigen via MHC class I molecules. 62. A method according to any one of claims 57 to 61 comprising contacting the sample with a second binding agent having affinity for a dendritic cell marker. 63. A method according to claim 62 wherein the dendritic cell marker is CDIl, preferably CDlIc, or HLA-DR, or BDCA-3. 64. A method according to claim 62 or claim 63 wherein only those cells to which both the first and second binding agents bind are identified or isolated. 65. A method according to any one of claims 57 to 64 comprising negative selection for one or more unwanted cell types. 66. A method according to claim 65 wherein the unwanted cell type is a subgroup of dendritic cells. 67. A method according to claim 66 wherein the unwanted cell type is plasmacytoid dendritic cells (pDCs) . 68. A method according to any one of claims 57- to 67 comprising determining the level of CLEC9a expression on the cells. 69. An antigen presenting cell or population thereof isolated by a method according to any one of claims 58 to 68. 70. A method of stimulating an immune response against a peptide antigen comprising providing an antigen presenting cell or population thereof according to claim 69, and contacting said cell or population of cells with said antigen. 71. A method according to claim 70 comprising administering the cell or population of cells to a subject. 72. A method according to claim 71 wherein the cells are re- administered to the subject from whom they were derived. 73. A method according to claim 71 or claim 72 further comprising contacting said cell or population of cells with an adjuvant . 74. A method according to claim 73 wherein the cell or population of cells is contacted with the adjuvant and antigen at substantially the same time. 75. A method according to claim 73 or claim 74 wherein the adjuvant is retinoic acid, a CD40 agonist or a TLR agonist or other immunostimulatory agent. 76. An antigen presenting cell or population thereof according to claim 69, for use in a method of medical treatment . 77. An antigen presenting cell or population thereof according to claim 69, for use in a method of stimulating an immune response against a target antigen. 78. Use of a primed antigen presenting cell or population thereof, obtained by a method according to claim 70, in the preparation of a medicament for the stimulation of an immune response against a target antigen. 79. A method according to claim 70 comprising, following said contacting step, contacting said antigen presenting cells with a population of cells comprising one or more T cells. 80. A method according to claim 79 comprising expanding the T cells in the population. 81. A method according to claim 79 or claim 80 comprising administering the T cells to a subject. 82. A method according to any one of claims 79 to 81 wherein the T cells and antigen presenting cells are autologous. 83. A method according to claim 82 wherein the T cells and antigen presenting cells are derived from the same subject. 84. A method according to claim 83 wherein the T cells are administered to the subject from whom they were derived. 85. A method according to any one of claims 81 to 84 comprising administering an adjuvant. 86. A method according to claim 85 wherein the adjuvant is retinoic acid, a CD40 agonist or a TLR agonist. 87. A method according to any one of claims 79 to 86 wherein the T cells comprise CTLs or helper T cells including Treg cells or Thl7 cells. 88. A T cell or population thereof, obtained by a method according to claim 79 or claim 80. 89. A T cell or population thereof according to claim 88, for use in a method of medical treatment. 90. A T cell or population thereof according to claim 88, for use in a method of stimulating an immune response against a target antigen. 91. Use of a T cell or population thereof according to claim 88, in the preparation of a medicament for the stimulation of an immune response against a target antigen. 92. A method for inducing tolerance in a subject towards an antigen, comprising administering to the subject a composition comprising the antigen, wherein the antigen is associated with a binding agent having affinity for CLEC9a, and wherein the antigen is administered in the absence of an adjuvant. 93. A composition according to any one of claims 7 to 9 for use in inducing tolerance in a subject towards said antigen. 94. Use of a composition according to any one of claims 7 to 9 in the preparation of a medicament for use in a method of inducing tolerance in a subject towards said antigen. 95. A method of screening for a physiological ligand for CLEC9a comprising contacting a target substance comprising the extracellular domain of CLEC9a or a portion thereof sufficient to bind CLEC9a ligand with a test substance which is a component of a mammalian cell, and determining binding of the target substance to the test substance. 96. A method according to claim 95 further comprising the step of identifying the test substance. 97. A method according to claim 95 or claim 96 wherein the test substance is an intracellular component of a mammalian cell. 98. A method according to any one of claims 95 to 97 wherein the test substance and CLEC9a or portion thereof present in the target substance are from the same species . 99. A method according to any one of claims 95 to 98 comprising the step of contacting the target substance with a sample comprising the test substance. 100. A method according to claim 99 wherein the sample comprises permeabilised mammalian cells. 101. A method according to claim 100 wherein the cells are fixed. 102. A method according to claim 100 or claim 101 comprising determining the subcellular location at which binding of the target substance takes place, by detection of the target substance . 103. A method according to claim 99 wherein the sample comprises a cell lysate, extract or a subcellular fraction of a mammalian cell. 104. A method according to any one of claims 95 to 103 comprising the step of isolating a complex comprising the target substance and the test substance. 105. A method according to any one of claims 95 to 103 wherein the test substance is immobilised on a solid support. 106. A method according to any one of claims 95 to 105 comprising identification of the test substance by proteomic techniques. 107. A method according to claim 95 wherein interaction between the test substance and target substance takes place in a cell or cell-free expression system and induces a detectable reaction such as expression of a reporter gene.
