Native and recombinant interleukin-2, two functionally distinct molecules.

Recombinant IL-2 (rIL-2) produced in prokaryotes, is widely used in lieu of native IL-2, which is secreted by T cells, to assess the functional profile of this cytokine. We provide evidence that a naturally occurring species of post-translationally modified IL-2 (moIL-2) exhibits enhanced bioactivity compared to rIL-2, as tested at the biochemical and functional level. We show that moIL-2 has high binding affinity for the IL-2 receptor (IL-2R), induces the immediate expression of the IL-2R alpha chain and rapidly activates downstream signaling molecules. Finally, in contrast to rIL-2, moIL-2 can promote the antigen-independent proliferation of resting lymphocytes. Collectively, our data demonstrate that native moIL-2 is functionally distinct from rIL-2, suggesting the existence of diverse IL-2 variants which may be critical for the shaping of the immune response.