A p74 common gamma receptor chain isoform facilitates IL-2 and IL-15 responses by the myelomonocytic cell line...

Functional forms of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors require the gamma c receptor component. We have described previously a myeloid cell line called Tf-1beta, which binds IL-2 with intermediate-affinity and proliferates in response to IL-2. In this study, we characterize gamma c expression on Tf-1beta2 cells, a derivative of Tf-1beta cells stimulated exclusively with IL-2. Although Tf-1beta2 cells bind IL-2 with intermediate-affinity and proliferate in response to IL-2, this cell line does not express the p64 gamma c chain at the protein level. This result was surprising because prior studies suggest these cells should not be expected to proliferate in response to IL-2 or IL-15 in the absence of the p64 gamma c chain. A p74 protein was detected by western blot following immunoprecipitation with an anti-gamma c polyclonal antibody, and a p74 protein was identified consistently in complex with IL-2 and IL-15 on these cells. However, the gamma c gene in these Tf-1beta2 cells shows no evidence of mutation by sequence analysis. Furthermore, inhibition of glycosylation of these Tf-1beta2 cells by tunicamycin treatment yields a standard 39-kDa molecule recognized on western blot with anti-gamma c antibody, as seen for the standard 64-kDa isoform of gamma c. These results demonstrate that a 74-kDa gamma c receptor isoform was involved in the response of the Tf-1beta2 cells to cytokines which normally interact with the 64-kDa gamma c chain.