The present invention relates to the identification of an epitope in human Interleukin-15 (IL-15) that is responsible for binding to the interleukin-15 receptor α-chain. Two IL-15 regions are involved in the formation of this epitope: the first region (44LLELQVISL52, peptide 1) corresponds to a sequence located in the B helix and the second (64ENLIL68, peptide 2 or 64ENLIIL69, peptide 2a) to a sequence located in helix C. Muteins displaying agonist or antagonist properties are described, and may be useful as therapeutic agents.