基本信息
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职业迁徙
个人简介
Research Areas
Infection and ImmunityCell Biology
My group studies the mechanisms by which leukocytes, such as T cells, use cell surface receptors to recognise infected or otherwise abnormal cells. The T cell receptor (TCR) plays a major role in this process by probing the surfaces of cells for the presence of 'foreign' peptides presented on MHC molecules in a peptide-MHC (pMHC) complex. A major focus of our work is to understand how the binding of TCRs to foreign pMHC leads to T cell activation. The first step in TCR signal transduction following ligand engagement is tyrosine phosphorylation of the TCR/CD3 complex, which we term triggering. Simon Davis and I have proposed a new mechanism of TCR triggering, termed the kinetic-segregation model. It postulates that TCR binding to pMHC segregates the TCR, and the tyrosine kinases that phosphorylate it, from tyrosine phosphatases with large extracellular domains such as CD45 and CD148. Unlike other proposed TCR triggering mechanisms this represents an entirely novel mechanism of signal transduction across membranes, delaying its acceptance. However, there is now a large body of evidence from my lab (e.g. Choudhuri et al, 2005 and Cordoba et al, 2013), Simon Davis's lab (Chang et al, 2016; Chen et al, 2021), and from several other labs (e.g. James & Vale, 2012; Schmidt et al, 2016) that strongly supports this model. Crucially, Chimeric Antigen Receptors (CARs) based on the TCR, which are transforming the treatment of cancer (e.g. using autologous T cells expressing CARs targeting cancer cells), also use the kinetic-segregation mechanism (Qian et al., 2022).
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论文共 216 篇作者统计合作学者相似作者
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biorxiv(2024)
Ashna Patel, V André, Sofía Bustamante Eguiguren,Michael I Barton,Eleanor M Denham,Johannes Pettmann,Alexander M. Mørch,Mikhail A. Kutuzov,Jesús A. Siller-Farfán,Michael L. Dustin,P. Anton van der Merwe,Omer Dushek
bioRxiv (Cold Spring Harbor Laboratory) (2023)
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biorxiv(2023)
Fenglei Li,Sobhan Roy, Jacob Niculcea,Keith Gould,Erin J Adams,P Anton van der Merwe,Kaushik Choudhuri
bioRxiv : the preprint server for biology (2023)
Proceedings of the National Academy of Sciences of the United States of Americano. 9 (2022)
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