RT info:eu-repo/semantics/article T1 Ligand-engaged TCR is triggered by Lck not associated with CD8 coreceptor A1 Casas, Javier A1 Brzostek, Joanna A1 Zarnitsyna, Veronika I. A1 Hong, Jin-sung A1 Wei, Qianru A1 Hoerter, John A. H. A1 Fu, Guo A1 Ampudia, Jeanette A1 Zamoyska, Rose A1 Zhu, Cheng A1 Gascoigne, Nicholas R. J. AB The earliest molecular events in T-cell recognition have not yet been fully described, and the initial T-cell receptor (TCR)-triggering mechanism remains a subject of controversy. Here, using total internal reflection/Forster resonance energy transfer microscopy, we observe a two-stage interaction between TCR, CD8 and major histocompatibility complex (MHC)-peptide. There is an early (within seconds) interaction between CD3ζ and the coreceptor CD8 that is independent of the binding of CD8 to MHC, but that requires CD8 association with Lck. Later (several minutes) CD3ζ–CD8 interactions require CD8–MHC binding. Lck can be found free or bound to the coreceptor. This work indicates that the initial TCR-triggering event is induced by free Lck. The early signalling events that trigger initial T-cell receptor signalling are not clearly defined. Here the authors show that this occurs in two stages, the first between the CD8 coreceptor and CD3 requiring Lck association to CD8, while the second interaction requires binding of major histocompatibility molecules. YR 2014 FD 2014 LK https://uvadoc.uva.es/handle/10324/64302 UL https://uvadoc.uva.es/handle/10324/64302 LA eng NO Nature Communications 5:5624. https://doi.org/10.1038/ncomms6624 NO Producción Científica DS UVaDOC RD 07-ago-2024