Human hematopoietic cells express two forms of the cytokine receptor common γ-chain (γc)

Recent studies have revealed that the γ-chain of the IL-2 receptor is shared by the receptors for IL-4, IL-7, IL-9, IL-13, and IL-15, and it is therefore also referred to as the common 7-chain (7c). Mutations of γc result in X-linked severe combined immunodeficiency syndrome in humans, indicating that γc is essential for normal development and function of the immune system. We demonstrate that human hematopoietic cells express two γc transcripts differing in their carboxyl terminal coding region. One transcript is the previously reported sequence (γc-long), whereas the newly identified sequence exhibits a deletion of 72 nucleotides close to the 3′-end of the open reading frame (γc-short). This alteration predicts a loss of 24 amino acids including a conserved tyrosine residue which is shared by several members of the cytokine receptor family. The presence of these two distinct forms of γc transcripts was demonstrated by sequencing of reversely transcribed and polymerase chain reaction (RT-PCR) amplified mRNA, restriction digestion of the RT-PCR products, RNAse protection, and Northern blotting from human cell lines and human peripheral blood lymphocytes. Furthermore, the two variants were present in peripheral blood lymphocytes from both female and male donors, which rules out allelic variants since γc is a single copy gene located on the X chromosome. A truncation mutant at a site near the observed changes in γG-short has been reported by others to alter biochemical events activated by cytokines. This combined with the loss of a potential SH2 "docking" site in γc-short suggests that γc-long and γc-short may link to different signaling pathways and may play an important role in determining the cellular response to IL-2, IL-4, IL-7, IL-9, IL-13, IL-15.