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<https://discovery.ucl.ac.uk/id/eprint/10203183> <http://purl.org/dc/terms/title> "Illuminating the role of the protein tyrosine phosphatase PTPN22 in actin remodelling by super-resolution microscopy: insights into T cell synapse formation"^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10203183> <http://purl.org/ontology/bibo/abstract> "Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) is a protein tyrosine phosphatase\r\noperating within the T cell signalling cascade. PTPN22 dephosphorylates key signalling proteins,\r\nin combination with the binding partner c-SRC kinase (Csk), which leads to downregulation of T\r\ncell activation. Associated with over 15 autoimmune diseases, PTPN22 R620W is one of the most\r\ncommon autoimmune disease related mutations. Recently, studies have uncovered a novel binding\r\npartner of PTPN22, proline-serine-threonine phosphatase interacting protein 1 (PSTPIP-1). Whilst\r\ndecades of research have focused on understanding the consequences of PTPN22 mutation in T cell\r\nactivation, the effects of the PTPN22-PSTPIP-1 interaction are poorly understood. PSTPIP-1 regulates F-actin remodelling via association with Wiskott-Aldrich syndrome protein (WASp). WASp\r\npromotes the formation of F-actin foci following T cell receptor (TCR) microcluster formation,\r\namplifying downstream TCR signals. Mutations within PSTPIP-1 are associated with autoinflammatory disorders and immunodeficiencies. These mutations correlate with defects in F-actin\r\nformation and lie within the PTPN22 binding domain, suggesting that PTPN22/PSTPIP-1 interactions regulate actin remodelling in T cells and thus T cell signalling. Using both live and fixed\r\nmulticolour 3D super-resolution imaging on a Spinning Disk Super Resolution by Optical Pixel\r\nReassignment (SoRa) microscope, this thesis describes a series of experiments exploiting Jurkat T\r\ncells deficient in PTPN22 expression and expressing T cell receptors reactive to ligands of different\r\naffinity. A key finding is that Jurkat T cells lacking PTPN22 exhibit aberrant actin remodelling\r\nalong with disrupted PSTPIP-1 and TCR clustering upon activation. The nanoscale organisation\r\nof PSTPIP-1 and TCR clusters at different Z-planes was visualised using single molecule localization DNA-PAINT microscopy on the SoRa microscope, coupled with quantitative PAINT analysis.\r\nThese results uncover a novel pathway involving PTPN22 and PSTPIP-1 in T cell signalling, providing new insight into the molecular mechanisms that underpin susceptibility to a wide range of\r\nautoimmune diseases."^^<http://www.w3.org/2001/XMLSchema#string> .
<https://discovery.ucl.ac.uk/id/eprint/10203183> <http://purl.org/dc/terms/date> "2025-01-28" .
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