Human and mouse CD137 have predominantly different binding CRDs to their respective ligands.
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.
Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
Ling
L
Yi
Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
Yanlin
Y
Zhao
Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
Xiaojue
X
Wang
Department of Pathology, Harborview Medical Center, University of Washington, Seattle, Washington, United States of America.
Min
M
Dai
Department of Pathology, Harborview Medical Center, University of Washington, Seattle, Washington, United States of America.
Karl Erik
KE
Hellström
Department of Pathology, Harborview Medical Center, University of Washington, Seattle, Washington, United States of America.
Ingegerd
I
Hellström
Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University and Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
Hongtao
H
Zhang
D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*
D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D003545:Cysteine