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Linhares, Annika De Sousa; Kellner, Florian; Jutz, Sabrina; Zlabinger, Gerhard J.; Gabius, Hans-Joachim; Huppa, Johannes B.; Leitner, Judith and Steinberger, Peter (2020): TIM-3 and CEACAM1 do not interact in cis and in trans. In: European Journal of Immunology, Vol. 50, No. 8: pp. 1126-1141

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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 in support of an interaction between TIM-3 and CEACAM1. Cytoplasmic sequences were 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.

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