Annual Review of Immunology Volume 27 2009 by Annual Reviews

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27. org by University of Bergen UNIVERSITETSBIBLIOTEKET on 01/13/09. For personal use only. 116. Nishimoto N, Kishimoto T. 2006. Interleukin 6: from bench to bedside. Nat. Clin. Pract. Rheumatol. 2:619–26 117. Maini RN, Taylor PC, Szechinski J, Pavelka K, Broll J, et al. 2006. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 54:2817–29 118.

A complex with three subunits, IL-2Rα, IL-2β, and γc , is the highaffinity complex (Kd ≈ 10 pM) for IL-2 and is the receptor form on activated T cells (101). The high-affinity receptor complex mediates most biological effects of IL-2 in vivo (102). Prior to structural analysis, the Ciardelli group published a series of elegant papers measuring the various rate constants and affinities for soluble forms of the different compositions of complexes (103–107). A similar analysis of the soluble complex assembly has also been conducted using thermodynamic measurements instead of kinetic studies (97).

15 ANRV371-IY27-02 ARI 18 September 2008 23:21 Binding site I in IL-2Rβ quaternary complex a Binding site I in IL-4Rα ternary complex Helix C CC'1 Helix B Helix A Helix C R42 Helix A N88 D20 R88 CC1' Annu. Rev. Immunol. 27. org by University of Bergen UNIVERSITETSBIBLIOTEKET on 01/13/09. For personal use only. EF1 H133 Y134 E9 D72 Y13 EF1 BC2 Y182 AB1 Binding site IIa in IL-2 quaternary complex b BC2 FG2 Binding site IIa in the IL-4 ternary complex Helix C CC1' Helix D CC1' Helix A EF1 E122 R121 Q126 Y103 Helix A Y124 C209 FG2 Helix D Y182 C160 γc BC2 L208 Y103 C209 C160 BC2 FG2 γc E122 S127 Y103 Q126 C209 C160 T118 S125 S130 I129 EF1 T123 Y124 Y103 C209 R121 C160 Figure 8 Specific versus degenerate binding sites I and IIa in the IL-2/IL-2Rα/IL-2Rβ/γc and IL-4/IL-4Rα/γc complexes.

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