Abstract
Monoclonal antibodies (mAbs) to CD137 (a.k.a. 4-1BB) have anti-tumor efficacy in several animal models and have entered clinical trials in patients with advanced cancer. Importantly, anti-CD137 mAbs can also ameliorate autoimmunity in preclinical models. As an approach to better understand the action of agonistic and antagonistic anti-CD137 mAbs we have mapped the binding region of the CD137 ligand (CD137L) to human and mouse CD137. By investigating the binding of CD137L to cysteine rich domain II (CRDII )and CRDIII of CD137, we found that the binding interface was limited and differed between the two species in that mouse CD137L mainly combined with CRDII and human CD137L mainly combined with CRDIII.
Highlights
CD137 belongs to the third group of receptors encoded by the TNF superfamily which includes OX40, CD27, CD30, and CD40
ELISA assays showed that mouse CD137 (mE),mE3 and mE4 bound to mCD137L while mE2 (CRDI) did not, and that mE3(CRDI+II) had the strongest binding
Human CRDI+cysteine rich domain II (CRDII) could not bind to human CD137 ligand (CD137L) while CRDI+ CRDII+CDDIII could
Summary
CD137 belongs to the third group of receptors encoded by the TNF superfamily which includes OX40, CD27, CD30, and CD40. These receptors are all costimulatory molecules and act at different stages in T and B cell activation to modulate the immune response [1,2,3]. Engagement of CD137 boosts proliferation of T cells, activates their effector functions, survival and establishes immunological memory [8]. Baessler and colleagues recently reported that the engagement of CD137 on mouse and human NK cells had opposite effects in that CD137 functions as an inhibitory receptor in humans and as a stimulatory receptor in mice [11]
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