| abstract |
The present invention relates to human interleukin-2 mutant capable of making human interleukin-2 and CD25 produce covalent cross-linking, and the long-acting human interleukin-2 mutant modified by these mutants. The interleukin-2 and the mutant thereof which generate covalent crosslinking activity with the CD25 can preferentially and durably activate regulatory T cells, and less or even not activate other effector cells, thereby playing a role in long-acting immunosuppression. The invention further relates to the use of such site-directed mutated or modified interleukin-2, e.g. as a stable, long-acting immunosuppressant for the treatment of various autoimmune diseases. After the IL-2 mutant obtained by the invention is combined with CD25, irreversible covalent crosslinking can be generated, and the recycling efficiency of IL-2 after internalization along with CD25 is greatly enhanced, so that the existence time and the action efficiency of IL-2 on Treg cells are increased. |