Fusion molecules and IL-15 variants
View Patent ↗The instant invention provides soluble fusion protein complexes and IL-15 variants that have therapeutic and diagnostic use, and methods for making the such proteins. The instant invention additionally provides methods of stimulating or suppressing immune responses in a mammal using the fusion protein complexes and IL-15 variants of the invention.
1. An isolated human interleukin 15 (hIL-15) variant comprising an amino acid substitution at position 61, 72, 92, or 111 of a mature human IL-15 sequence of SEQ ID NO:1, wherein the hIL-15 variant has increased or decreased binding activity for the interleukin 15 receptor beta/gamma chain (IL-15RβγC) receptors compared to native hIL-15 polypeptide.
2. The isolated hIL-15 variant of claim 1 , wherein the hIL-15 variant functions as an IL-15 agonist or antagonist.
3. The isolated hIL-15 variant of claim 1 , where the amino acid substitution is in the domain of IL-15 that interacts with IL-15RβγC, or both IL-15Rβ and γC.
4. The isolated hIL-15 variant of claim 1 , wherein the amino acid substitution is of D to A at position 61 or N to R at position 72 of the mature human IL-15 sequence.
5. The isolated hIL-15 variant of claim 4 , wherein the amino acid substitution results in an hIL-15 variant that has IL-15 antagonist activity or decreased binding activity for the IL-15RβγC receptors compared to the native hIL-15 polypeptide.
6. The isolated hIL-15 variant of claim 1 , wherein the amino acid substitution is of N to D at position 72 of the mature human IL-15 sequence.
7. The isolated hIL-15 variant of claim 6 , wherein the amino acid substitution results in an IL-15 variant that has IL-15 agonist activity or increased binding activity for the IL-15RβγC receptors compared to the native hIL-15 polypeptide.
8. An isolated human interleukin 15 (hIL-15) variant, comprising an amino acid substitution at position 72 of a mature human IL-15 sequence.
9. The isolated hIL-15 variant of claim 8 , wherein the amino acid substitution is selected from the group consisting of alanine, aspartic acid, and arginine.