Receptor on the surface of activated T-cells: ACT-4
OwnerWayne Godfrey, David Buck +1inventors
InventorsWayne Godfrey, David Buck, Edgar G. Engleman
Life of this patent
Estimating the term…
Abstract
The invention provides purified ACT-4 receptor polypeptides, antibodies against these polypeptides and nucleic acids encoding ACT-4 receptor polypeptides. Also provided are methods of diagnosis and treatment using the same. ACT-4 receptors are preferentially expressed on the surface of activated CD4+ T-cells. ACT-4 receptors are usually expressed at low levels on the surface of activated CD8+ cells, and are usually substantially absent on resting T-cells, and on monocytes and B-cells (resting or activated). An exemplary ACT-4 receptor, termed ACT-4-h-1, has a signal sequence, an extracellular domain comprising three disulfide-bonded intrachain loops, a transmembrane domain, and an intracellular domain.
Claims58
A purified ACT-4 receptor polypeptide that comprises at least five contiguous amino acids from an amino acid sequence shown in FIG. 5.
A polypeptide consisting essentially of an epitope specifically bound by an antibody designated L106.
An antibody that specifically binds to an ACT-4-h-1 receptor polypeptide.
A humanized antibody comprising a humanized heavy chain and a humanized light chain:
- (1) the humanized light chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of a L106 antibody light chain, and having a variable region framework sequence substantially identical to a human light chain variable region framework sequence;
- and
- (2) the humanized heavy chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of a L106 antibody heavy chain, and having a variable region framework sequence substantially identical to a human heavy chain variable region framework sequence;
- wherein the humanized antibody specifically binds to an ACT-4-h-1 receptor polypeptide with a binding affinity that is within three-fold of the binding affinity of a L106 antibody.
A hybridoma producing antibody L106, said hybridoma deposited as ATCC______.
A method of screening an antibody for specific binding to the same epitope as that bound by an L106 antibody, said method comprising:
- providing a solution comprising an antibody to be screened, said L106 antibody, and an ACT-4-h-1 receptor polypeptide, said polypeptide specifically binding to said L106 antibody;
- and
- measuring specific binding between said polypeptide and said L106 antibody, or between said polypeptide and said antibody to be screened, to indicate whether said antibody to be screened reacts with the same epitope as said L106 antibody.
A method of localizing an epitope specifically bound by an L106 antibody, said method comprising:
- providing a family of ACT-4-h-1 receptor polypeptides, each member of said family comprising a contiguous segment of at least four amino acids;
- and
- measuring specific binding between a polypeptide from said family and said L106 antibody to indicate the presence of said epitope within said polypeptide.
A method of screening for immunosuppressive agents, said method comprising:
- contacting an ACT-4-h-1 receptor polypeptide with a potential immunosuppressive agent;
- and
- detecting specific binding between said ACT-4-h-1 receptor polypeptide and said agent, said specific binding indicative of immunosuppressive activity.
A method for screening for an ACT-4 ligand, said method comprising:
- contacting a biological sample containing said ACT-4 ligand with an ACT-4-h-1 receptor polypeptide;
- isolating a complex formed between said ligand and said ACT-4-h-1 receptor polypeptide;
- and
- dissociating said complex to obtain said ligand.
An ACT-4 ligand that specifically binds to an ACT-4-h-1 receptor polypeptide.
Dependencies are inferred from the claim text.