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Unstimulated Human CD4 Lymphocytes Express a Cytoplasmic Immature Form of the Common Cytokine Receptor -Chain¹

Lynda Bani^*, Virginie Pasquier^2,*, Marko Kryworuchko^2,*, Jean Salamero and Jacques Thèze^3,*

^* Unité d’Immunogénétique Cellulaire, Département d’Immunologie, Institut Pasteur; and Unité Mixte de Recherche, Centre National de la Recherche Scientifique 144, Laboratoire "Mécanismes Moléculaires du Transport Intracellulaire" Institut Curie, Paris, France

As a component of various cytokine receptors, common cytokine receptor -chain (_c) 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 _c (64 kDa) recognized by mAb Tugh4. However, these cells constitutively transcribe the corresponding _c gene. This apparent paradox was solved by the demonstration that polyclonal anti-_c Abs detected endoglycosidase-H-sensitive immature forms of _c (54–58 kDa) expressed by quiescent CD4 T lymphocytes and Jurkat cells. Immature _c is characterized as an intracellular component localized in the endoplasmic reticulum. Pulse-chase analysis shows that the immature _c 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 _c 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 _c may require intracellular interactions with lineage- or subset-specific molecular partners.

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