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Publications in T-Cell Antigen Receptor by NOMIS researchers

Protocol to determine antibody affinity and concentration in complex solutions using microfluidic antibody affinity profiling

NOMIS Researcher(s)

Published in

March 17, 2023

Conventional methods of measuring affinity are limited by artificial immobilization, large sample volumes, and homogeneous solutions. This protocol describes microfluidic antibody affinity profiling on complex human samples in solution to obtain a fingerprint reflecting both affinity and active concentration of the target protein. To illustrate the protocol, we analyze the antibody response in SARS-CoV-2 omicron-naïve samples against different SARS-CoV-2 variants of concern. However, the protocol and the technology are amenable to a broad spectrum of biomedical questions. For complete details on the use and execution of this protocol, please refer to Emmenegger et al. (2022),1 Schneider et al. (2022),2 and Fiedler et al. (2022).3 © 2023 The Author(s)

Research field(s)
Health Sciences, Biomedical Research, Developmental Biology

DOI
10.1016/j.xpro.2023.102095

T cell receptor dwell times control the kinase activity of Zap70

NOMIS Researcher(s)

Published in

August 19, 2015

Kinase recruitment to membrane receptors is essential for signal transduction. However, the underlying regulatory mechanisms are poorly understood. We investigated how conformational changes control T cell receptor (TCR) association and activity of the kinase Zap70. Structural analysis showed that TCR binding or phosphorylation of Zap70 triggers a transition from a closed, autoinhibited conformation to an open conformation. Using Zap70 mutants with defined conformations, we found that TCR dwell times controlled Zap70 activity. The closed conformation minimized TCR dwell times and thereby prevented activation by membrane-associated kinases. Parallel recruitment of coreceptor-associated Lck kinase to the TCR ensured Zap70 phosphorylation and stabilized Zap70 TCR binding. Our study suggests that the dynamics of cytosolic enzyme recruitment to the plasma membrane regulate the activity and function of receptors lacking intrinsic catalytic activity.

Research field(s)
Health Sciences, Clinical Medicine, Immunology

DOI
10.1038/ni.3231

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