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Ligand engaged TCR is triggered by active Lck not associated with coreceptor

Casas, J and Brzostek, J and Zarnitsyna, V and Hong, JS and Hoerter, J and Ampudia, J and Zamoyska, R and Zhu, C and Gascoigne, N (2014) Ligand engaged TCR is triggered by active Lck not associated with coreceptor. Nature Communications.

Abstract

The earliest molecular events in T cell recognition have not yet been fully described, and
the initial TCR triggering mechanism remains a subject of controversy. Using
TIRF/FRET microscopy we observed a two-stage interaction between TCR, CD8, and
MHCp. 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. In mature CD8 T cells we find
that the activated population of Lck is not coreceptor-associated. This work indicates that
the initial TCR triggering event is induced by free Lck.

Item Type: Article
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/23836

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