IL-2 and Its Receptor

Structure of the IL-2 Receptor

The IL-2 receptor is a heterotrimeric receptor, composed of a high affinity cytokine binding subunit (IL-2R α chain, CD25) and two signaling components, the IL-2 receptor β chain the the common receptor γ chain (γc) that is shared with the IL-4, IL-7, IL-9, and IL-15 receptors. These receptor chains activate cytokine specific signaling pathways, such as those transduced by the actviation of Janus kinases (Jaks) and signal transducers and activators of transcription (Stats), as well as general signaling pathways, that are implicated in cell proliferation and differentiation. The IL-2 receptor also recruits the adapter protein Shc, linking it to the Ras/MAP kinase and PI-3 kinase/Akt pathways.

Three IL-2 receptor chains have been identified: IL-2Rα (CD25, Tac), IL-2Rβ, adn the common γ (γc) chain. These chains combine to form 3 different IL-2 receptor complexes distinguished by their binding affinity for IL-2; the low affinity alphay chain only, intermediate afficinity (alpha and beta), and high affinity (alpha, beta and γc chains) receptors. The cytoplasmic domain of the beta chain is essential for signal transduction in response to IL-2, such that only the intermediate and high affinity receptors are able to transduce the IL-2 signals.

Functions

IL-2 type 1 cytokine that is the exclusive product of T cells. It binds to IL-2 receptors expressed on resting and activated mononuclear cells, and is critical to the hosts' normal cellular and humoral immune response.

IL-2 may have both positive and negative effects on T cells. Il-2 is required for propagation of T-cell clones in vitro and can promote T-cell survival by increasing expression of anti-apoptotic proteins, including Bcl-2.  However, Il-2 can also cause effector T cells to undergo activation-induced cell death.

IL-2 is the earliest cytokine secreted by naive Thp cells and is an overall growth factor for both T-helper subsets but is especially important for Th2 development.

Il-2 is currently used to enhance T-cell responses to viral and tumor antigens in patients, including those with HIV or metastatic cancer. High-dose IL-2 therapy, however, is limited by its toxicity resulting from vascular leakage. IL-2 has been previously reported to modulate CD95-mediated CD4 T-cell death in both HIV-infected individuals and SIV-infected macaques.

Due to its short in vivo half-life, IL-2/Ig fusion protein has been developed and showed to increase DNA vaccination efficacy, CD4+ T cell activation and proliferation. In addition IL-2 administration has been shown to induce HIV peptide specific and non-specific IFN-y producing cells, memory T cells and NK Cells.

IL-2, along with IL-12, enhance IFN-γ synthesis.