Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination

0511345 - ÚMG 2020 RIV US eng J - Článek v odborném periodiku
Lo, W.L. - Shah, N.H. - Rubin, S. A. - Zhang, W. - Horková, Veronika - Fallahee, I. R. - Štěpánek, Ondřej - Zon, L.I. - Kuriyan, J. - Weiss, A.
Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.
Nature Immunology. Roč. 20, č. 11 (2019), s. 1481-1493. ISSN 1529-2908. E-ISSN 1529-2916
Grant CEP: GA ČR GJ19-03435Y
Institucionální podpora: RVO:68378050
Klíčová slova: homology 2 domain * lymphoproliferative disease * phospholipase c-gamma-1 * signaling complexes * self-peptides * activation * receptor * tcr * linker * binding
Obor OECD: Immunology
Impakt faktor: 20.479, rok: 2019
Způsob publikování: Omezený přístup
https://www.nature.com/articles/s41590-019-0502-2

Self-non-self discrimination is central to T cell-mediated immunity. The kinetic proofreading model can explain T cell antigen receptor (TCR) ligand discrimination, however, the rate-limiting steps have not been identified. Here, we show that tyrosine phosphorylation of the T cell adapter protein LAT at position Y132 is a critical kinetic bottleneck for ligand discrimination. LAT phosphorylation at Y132, mediated by the kinase ZAP-70, leads to the recruitment and activation of phospholipase C-gamma 1 (PLC-gamma 1), an important effector molecule for T cell activation. The slow phosphorylation of Y132, relative to other phosphosites on LAT, is governed by a preceding glycine residue (G131) but can be accelerated by substituting this glycine with aspartate or glutamate. Acceleration of Y132 phosphorylation increases the speed and magnitude of PLC-gamma 1 activation and enhances T cell sensitivity to weaker stimuli, including weak agonists and self-peptides. These observations suggest that the slow phosphorylation of Y132 acts as a proofreading step to facilitate T cell ligand discrimination.
Trvalý link: http://hdl.handle.net/11104/0306727