EP 1023446 A1 20000802 - MUTEINS OF INTERLEUKIN 4 SHOWING LOW-AFFINITY AND SHORT-TERM INTERACTION WITH THE COMMON $g(g) CHAIN
Title (en)
MUTEINS OF INTERLEUKIN 4 SHOWING LOW-AFFINITY AND SHORT-TERM INTERACTION WITH THE COMMON $g(g) CHAIN
Title (de)
INTERLEUKIN-4 MUTEINE MIT NIEDRIGEN AFFINITÄT UND EINER KURZZEIT-WECHSELWIRKUNG MIT DER GAMMA C-KETTE
Title (fr)
MUTEINES D'INTERLEUKINE 4 PRESENTANT UNE INTERACTION A FAIBLE AFFINITE ET A COURT TERME AVEC LA CHAINE $g(g) COMMUNE
Publication
Application
Priority
- EP 98951511 A 19981012
- EP 9806448 W 19981012
- EP 97118219 A 19971021
Abstract (en)
[origin: EP0911401A1] Human IL-4 (IL-4), one of the small 4-helix-bundle cytokines, uses the specific IL-4 receptor a chain together with a promiscuous subunit, the common gamma chain ( gamma c) for transmembrane signaling. The ligand-binding properties of gamma c, which are presently poorly understood, were analysed by biosensor techniques employing recombinant ectodomains gamex ( gamma c) and IL4-BP (a) of the receptor chains. The formation and decay of a ternary complex between solute gamex and IL-4 liganded IL4-BP could be established to exhibit a low affinity (Kd = 3 mu M) as well as a short half life t1/2 = 7s. This binding affinity resulted to the major part from the interaction of gamex with IL-4 and not from a direct contact of IL4-BP and gamex, since the binary complex between solute gamex and immobilized IL-4 showed an only 50fold greater Kd of 150 mu M. The IL-4 residues involved in gamex binding were identified by means of an alanine-scanning mutational approach. A functional gamex binding IL-4 epitope is proposed comprising I11, N15, and Y124 as major determinants. Even IL-4 variants which bind gamex 300fold weaker than IL-4 with a dissociation half life t1/2 of less than 1s, retained a substantial T-cell proliferative activity. These findings suggest that low affinity gamma c binding and short half lives of the heterodimeric a/ gamma c receptor complex are sufficient for initiating IL-4 dependent signal transduction.
IPC 1-7
IPC 8 full level
C07K 14/54 (2006.01); C12N 1/15 (2006.01); C12N 1/19 (2006.01); C12N 1/21 (2006.01); C12N 5/10 (2006.01); C12N 15/09 (2006.01); C12N 15/24 (2006.01); C12P 21/00 (2006.01)
CPC (source: EP)
C07K 14/5406 (2013.01)
Citation (search report)
See references of WO 9920765A1
Designated contracting state (EPC)
DE ES FR GB IT
DOCDB simple family (publication)
EP 0911401 A1 19990428; AR 016147 A1 20010620; AU 9749598 A 19990510; EP 1023446 A1 20000802; JP 2001520040 A 20011030; WO 9920765 A1 19990429; ZA 989540 B 19990422
DOCDB simple family (application)
EP 97118219 A 19971021; AR P980105234 A 19981020; AU 9749598 A 19981012; EP 9806448 W 19981012; EP 98951511 A 19981012; JP 2000517085 A 19981012; ZA 989540 A 19981020