Interleukin-2 mediated activation of jak3 in the absence of a detectable 04 kda common 7 chain

The common 7 chain is a component of the interîeukin (IL)-2, IL-4, IL-7, IL-9, and IL-15 receptors. The central role of the common 7 chain in cytokine signaling is reflected by the fact that patients with mutations in the common 7 gene are affected with X-linked severe combined immune deficiency (SCID). One important mechanism by which the common 7 chain activates cytokine signal transduction is via the associated kinase JAK3. Recently, it has been demonstrated that mutations in the JAK3 gene can lead to autosomal SCID, a disease that phenotypically mimics X-linked SCID. This result underscores the importance of JAK3 in immune cell activation. In this study, we evaluate IL-2 responses by the Tf-1/3 cell line, an IL-2 receptor /?-expressing derivative of the myelomonocytic cell line Tf-1. Cellular proliferation occurs in an IL-2 dependent manner. However, a 64 IcDa common 7 chain was not detected in these cells, using either surface iodination or western blotting techniques which detect a 64 kDa common 7 chain in other cell types. Nevertheless, JAK3 phosphorylation by Tf-1/9 cells is induced by IL-2. Our results suggest the presence of a functional common 7 chain isoform of a different molecular weight in Tf-1/3 cells, but would also be consistent with the existence of a separate JAK3 activator induced in Tf-1/3 by IL-2.