Relevance of Nck-CD3 epsilon interaction for T cell activation in vivo

27.01.2014

Borroto A, Arellano I, Blanco R, Fuentes M, Orfao A, Dopfer EP, Prouza M, Suchànek M, Schamel WW, Alarcón B

J Immunol. 2014;192(5):2042-53

J Immunol.          online article

In this BIOSS publication the Schamel group cooperated with the group of Balbino Alarcon in Madrid to study the involvement of the CD3? proline?rich sequence (PRS) in T cell activation in vitro and in vivo. We used a knock?in mouse line bearing point mutations on the two central prolines in this PRS, preventing the recruitment of the adaptor protein Nck to CD3?. This mutation prevented T cell receptor (TCR)/CD3? induced activation of the T cells, indicating that the PRS is crucial for the activation of the TCR/CD3. We found a deficient anti?tumoral response in those mutant mice, and that they were partly protected against the development of neurological symptoms in an experimental autoimmune encephalitis model. Thus, our data suggest that Nck recruitment to the TCR is fundamental to mount an efficient T cell response in vivo, and that the Nck?CD3? interaction may represent a target for pharmacological modulation of the immune response.