Human IL-Rbeta chains form IL-2 binding homodimers.
Two types of functional interleukin-2 receptor (IL-2Ralpha/IL-2Rbeta/gammac and IL-2Rbeta/gammac) have already been characterized in humans. Here we describe a new form consisting of IL-2Rbeta/beta homodimers that assemble spontaneously in the absence of gammac. Co-transfection of COS-7 cells with constructs expressing IL-2Rbeta chains tagged with either HA or MYC sequences results in the formation of IL-2Rbeta:HA/IL-2Rbeta:MYC complexes detectable by coimmunoprecipitation. The formation of these IL-2Rbeta:HA/IL-2Rbeta:MYC dimers is also observed in the absence of IL-2. Moreover, in COS cells expressing chimeras of IL-2Rbeta fused to fluorescence reporters such as IL-2Rbeta:ECFP and IL-2Rbeta:EYFP, we also observed specific FRET at the surface of living cells, as expected for dimer formation. Transiently transfected COS-7 cells expressing IL-2Rbeta bind 125I-labeled IL-2 (homodimers, Kd = 1nM) as cells expressing both IL-2Rbeta and gammac chains (heterodimers, Kd = 1 nM). IL-2Rbeta/IL-2Rbeta could represent either a decoy receptor or a new form of IL-2R involved in signaling when gammac expression is low.
Pillet
Anne-Hélène
AH
Unité d'Immunogénétique Cellulaire, Département Infection et Epidémiologie, Institut Pasteur, Paris, France.
Juffroy
Olivier
O
Mazard-Pasquier
Virginie
V
Moreau
Jean-Louis
JL
Gesbert
Franck
F
Chastagner
Patricia
P
Colle
Jean-Hervé
JH
Thèze
Jacques
J
Rose
Thierry
T
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry* / Q000235:genetics; D053646:Interleukin-2 Receptor beta Subunit / Q000737:chemistry* / Q000235:genetics; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection
D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit