B7-h3 and b7-h4, novel immunoregulatory molecules
AssigneeMayo Foundation for Medical Education and Research
InventorLieping Chen
Life of this patent
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Abstract
The invention provides novel B7-H3 and B7-H4 polypeptides useful for co-stimulating T cells, isolated nucleic acid molecules encoding them, vectors containing the nucleic acid molecules, and cells containing the vectors. Also included are methods of making and using these co-stimulatory polypeptides.
Claims26
An isolated DNA comprising:
- (a) a nucleic acid sequence that encodes a polypeptide with the ability to co-stimulate a T cell, wherein the nucleic acid sequence hybridizes, after a wash at 50° C. to 65° C. in a buffer containing 0.2×SSC and 0.1% SDS, to the complement of the nucleotide sequence set forth in SEQ ID NO:6;
- or
- (b) the complement of the nucleic acid sequence.
An isolated nucleic acid comprising:
- (a) a nucleotide sequence that encodes a polypeptide comprising amino acids 34-282 of the amino acid sequence set forth in SEQ ID NO:5;
- or (b) the complement of the nucleotide sequence.
-19. (canceled)
A nucleic acid molecule encoding a fusion protein comprising a first domain joined to at least one additional domain, wherein the first domain comprises a co-stimulatory polypeptide encoded by a DNA comprising:
- (a) a nucleic acid sequence that encodes a polypeptide with the ability to co-stimulate a T cell, wherein the nucleic acid sequence hybridizes, after a wash at 50° C. to 65° C. in a buffer containing 0.2×SSC and 0.1% SDS, to the complement of the nucleotide sequence set forth in SEQ ID NO:6, or
- (b) the complement of the nucleic acid sequence.
A method of co-stimulating a T cell, the method comprising contacting the T cell with a polypeptide encoded by a DNA comprising:
- (a) a nucleic acid sequence that encodes a polypeptide with the ability to co-stimulate a T cell, wherein the nucleic acid sequence hybridizes, after a wash at 50° C. to 65° C. in a buffer containing 0.2×SSC and 0.1% SDS, to the complement of the nucleotide sequence set forth in SEQ ID NO:6;
- or
- (b) the complement of the nucleic acid sequence.
A method of identifying a compound that inhibits an immune response, the method comprising:
- (a) providing a test compound;
- (b) culturing, together, the compound, a polypeptide, a T cell, and a T cell activating stimulus;
- and
- (c) determining whether the test compound inhibits the response of the T cell to the stimulus, as an indication that the test compound inhibits an immune response,
- wherein the polypeptide is encoded by a DNA comprising:
- (i) a nucleic acid sequence that encodes a polypeptide with the ability to co-stimulate a T cell, wherein the nucleic acid sequence hybridizes, after a wash at 50° C. to 65° C. in a buffer containing 0.2×SSC and 0.1% SDS, to the complement of the nucleotide sequence set forth in SEQ ID NO:6;
- or
- (ii) the complement of the nucleic acid sequence.
A method of identifying a compound that enhances an immune response, the method comprising:
- (a) providing a test compound;
- (b) culturing, together, the compound, a polypeptide, a T cell, and a T cell activating stimulus;
- and
- (c) determining whether the test compound enhances the response of the T cell to the antigen, as an indication that the test compound enhances an immune response,
- wherein the polypeptide is co-stimulatory and is encoded by a DNA comprising:
- (i) a nucleic acid sequence that encodes a polypeptide with the ability to co-stimulate a T cell, wherein the nucleic acid sequence hybridizes, after a wash at 50° C. to 65° C. in a buffer containing 0.2×SSC and 0.1% SDS, to the complement of the nucleotide sequence set forth in SEQ ID NO:6;
- or
- (ii) the complement of the nucleic acid sequence.
A method of co-stimulating a T cell, the method comprising contacting the T cell with:
- (a) a first co-stimulatory polypeptide selected from the group consisting of (i) B7-H1, (ii) B7-H2, (iii) B7-H3, (iv) B7-H4, (v) a functional fragment of any of (i)-(iv), and (vi) any of (i)-(v) but with one or more conservative substitutions;
- and
- (b) one or more additional co-stimulatory polypeptides selected from the group consisting of (vi) B7-1, (vii) B7-2, (viii) B7-H1, (ix) B7-H2, (x) B7-H3, (xi) B7-H4, (xii) a functional fragment of any of (vi)-(xi), and (xii) any of (vi)-(xii) but with one or more conservative substitutions.
Dependencies are inferred from the claim text.