Lynda Bani

Unstimulated Human CD4 Lymphocytes Express a Cytoplasmic Immature Form of the Common Cytokine Receptor γ-Chain

As a component of various cytokine receptors, common cytokine receptor γ-chain (γc) is essential in the development of the immune system and plays an important role in different stages of inflammatory and immune responses. Here we establish that resting CD4 T cells and the Jurkat CD4 T cell line do not express the mature form of γc (64 kDa) recognized by mAb Tugh4. However, these cells constitutively transcribe the corresponding γc gene. This apparent paradox was solved by the demonstration that polyclonal anti-γc Abs detected endoglycosidase-H-sensitive immature forms of γc (54–58 kDa) expressed by quiescent CD4 T lymphocytes and Jurkat cells. Immature γc is characterized as an intracellular component localized in the endoplasmic reticulum. Pulse-chase analysis shows that the immature γc is rapidly degraded after synthesis. After activation of CD4 T lymphocytes, and as seen in the CD4 T cell line Kit 225, the endoglycosidase-H-resistant mature form of γc is detectable at the cell surface and in the endosomal compartment. For the first time, our results demonstrate that a cytokine receptor chain may be constitutively produced as an immature form. Furthermore, this supports the notion that expression of the functional form of γc may require intracellular interactions with lineage- or subset-specific molecular partners.