TIM-3 and CEACAM1 do not interact in cis and in trans.
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.
['De Sousa Linhares|Annika|A|', 'Kellner|Florian|F|0000-0001-5931-3798', 'Jutz|Sabrina|S|', 'Zlabinger|Gerhard J|GJ|0000-0002-7478-4173', 'Gabius|Hans-Joachim|HJ|', 'Huppa|Johannes B|JB|0000-0003-2634-8198', 'Leitner|Judith|J|0000-0002-7156-1759', 'Steinberger|Peter|P|0000-0001-6848-4097']
D015703:Antigens, CD D015815:Cell Adhesion Molecules D031541:Fluorescence Resonance Energy Transfer D057809:HEK293 Cells D000072597:Hepatitis A Virus Cellular Receptor 2 D006801:Humans D019169:Jurkat Cells D008213:Lymphocyte Activation D015398:Signal Transduction D013601:T-Lymphocytes
TIM-3 CEACAM1 Coinhibition Costimulation T-cell activation