|
|||||
|
|
TIM-3 and CEACAM1 do not interact in cis and in trans |
|
| Authors: | Annika De Sousa Linhares Florian Kellner Sabrina Jutz Gerhard J. Zlabinger Hans-Joachim Gabius Johannes B. Huppa Judith Leitner Peter Steinberger |
| Affiliation: | 1. Division of Immune Receptors and T Cell Activation, Center for Pathophysiology, Infectiology, and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria;2. Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria;3. Division of Clinical and Experimental Immunology, Center for Pathophysiology, Infectiology, and Immunology, Institute of Immunology, Medical University of Vienna, Vienna, Austria;4. Faculty of Veterinary Medicine, Institute for Physiological Chemistry, Ludwig-Maximilians-University, Munich, Germany |
| Abstract: | TIM-3 has been considered as a target in cancer immunotherapy. In T cells, inhibitory as well as activating functions have been ascribed to this molecule. Its role may therefore depend on the state of T cells and on the presence of interaction partners capable to perform functional pairing. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) has been proposed to bind TIM-3 and to regulate its function. Using a T cell reporter platform we confirmed CEACAM1-mediated inhibition, but CEACAM1 did not functionally engage TIM-3. TIM-3 and CEACAM1 coexpression was limited to a small subset of activated T cells. Moreover, results obtained in extensive binding studies were not in support of an interaction between TIM-3 and CEACAM1. Cytoplasmic sequences derived from TIM-3 induced inhibitory signaling in our human T cell reporter system. Our results indicate that TIM-3 functions are independent of CEACAM1 and that this receptor has the capability to promote inhibitory signaling pathways in human T cells. |
| Keywords: | CEACAM1 Coinhibition Costimulation T-cell activation TIM-3 |