Cd8 as an inhibitor of the cellular immune system
AssigneeAvidex Limited
InventorsBent Jakobsen, George Gao, Ulrich Gerth, Andrew Sewell
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Abstract
This invention is directed to a method for inhibiting cytotoxic T lymphocyte (CTL) activity in which soluble CD8 is used as the inhibitor. The invention is further directed to soluble forms of the CD8 molecule which can be administered to a patient. The method of this invention is particularly useful for immunosuppressive therapy in which inhibition of CTL activity is desirable, for example, in patients undergoing transplantation.
Claims15
A method for inhibiting activity of a T lymphocyte against a target cell, which method comprises contacting the target cell with a soluble form of a human CD8 molecule which has no specific antigen-binding capability other than that of native CD8 and which is folded as a dimer and has the property of inhibiting the action of cytotoxic T cell lymphocytes to kill target cells, wherein at least one α chain of said molecule (a) has SEQ ID NO:24 or (b) differs from SEQ ID NO:24 in one or more of the following respects:
- (i) methionine is absent at the N-terminus;
- (ii) 1-15 amino acid residues are absent from the N-terminus;
- (iii) part or all of SEQ ID NO:27 is added at the N-terminus;
- (iv) 1-15 amino acids are absent from the C-terminus;
- but with at least a part of the region defined by amino acid residues 116-120 retained;
- (v) part or all of SEQ ID NO:28 is added at the C-terminus;
- (vi) the addition of a protein or peptide, at the N or C terminus, for the purpose of purification;
- (vii) the provision of a label for detection.
A method of treatment of autoimmune disease comprising administering to a subject in need thereof an effective amount of a CD8αα molecule lacking a CD8 transmembrane domain but including a CD8 immunoglobulin domain and having no specific antigen-binding capability other than that of native CD8.
Dependencies are inferred from the claim text.