Various methods and compositions are provided which can be employed to modulate the immune system. Compositions include a fusion protein comprising: (a) a first polypeptide comprising Interleukin-2 (IL-2) or a functional variant or fragment thereof; and (b) a second polypeptide, fused in frame to the first polypeptide, wherein the second polypeptide comprises an extracellular domain of Interleukin-2 Receptor alpha (IL-2Rα) or a functional variant or fragment thereof, and wherein the fusion protein has IL-2 activity. Various methods are provided for modulating the immune response in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the IL-2/IL-2Rα fusion protein disclosed herein.