5UTZ

Human IL-2/Fab complex

Summary for 5UTZ

• Entry DOI: 10.2210/pdb5utz/pdb
• Descriptor: Fab 5111 heavy chain, Fab 5111 light chain, Interleukin-2, ... (5 entities in total)
• Functional Keywords: cytokine, fab, complex, cytokine-immune system complex, cytokine/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 12
• Total formula weight: 249703.99

Authors

Jude, K.M.,Garcia, K.C. (deposition date: 2017-02-15, release date: 2018-07-11, Last modification date: 2024-11-13)

Primary citation

Trotta, E.,Bessette, P.H.,Silveria, S.L.,Ely, L.K.,Jude, K.M.,Le, D.T.,Holst, C.R.,Coyle, A.,Potempa, M.,Lanier, L.L.,Garcia, K.C.,Crellin, N.K.,Rondon, I.J.,Bluestone, J.A.
A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism.
Nat. Med., 24:1005-1014, 2018

PubMed Abstract: Interleukin-2 (IL-2) has been shown to suppress immune pathologies by preferentially expanding regulatory T cells (T). However, this therapy has been limited by off-target complications due to pathogenic cell expansion. Recent efforts have been focused on developing a more selective IL-2. It is well documented that certain anti-mouse IL-2 antibodies induce conformational changes that result in selective targeting of T. We report the generation of a fully human anti-IL-2 antibody, F5111.2, that stabilizes IL-2 in a conformation that results in the preferential STAT5 phosphorylation of T in vitro and selective expansion of T in vivo. When complexed with human IL-2, F5111.2 induced remission of type 1 diabetes in the NOD mouse model, reduced disease severity in a model of experimental autoimmune encephalomyelitis and protected mice against xenogeneic graft-versus-host disease. These results suggest that IL-2-F5111.2 may provide an immunotherapy to treat autoimmune diseases and graft-versus-host disease.

PubMed: 29942088
DOI: 10.1038/s41591-018-0070-2

Experimental method

X-RAY DIFFRACTION (2.747 Å)