A p74 common gamma receptor chain isoform facilitates IL-2 and IL-15 responses by the myelomonocytic cell line Tf-1β2

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