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In his inaugural article in the Proceedings of the National Academy of Sciences as an NAS member (elected 2021), Prof Mike Dustin and his research team in Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences have explained how messages are passed across the immunological synapse. The research could have implications for future vaccine development and immunotherapy treatments.

TCR vesicles
An activated CD4+ T cell (white) has pushed T cell receptor loaded extracellular vesicles (cyan) onto an antigen presenting cell (APC) and pulled antigen (magenta) from the APC into the T cell.

The work started with Audun Kvalvaag's interest in clathrin, a protein that is well known for its role in bringing substances such as cholesterol and iron into cells for nutrition, and to generate small packages of information that can be released from cells called exosomes. Dr. Kvalvaag, a visiting scholar from Oslo, Norway, led the team in Dustin's lab that identified new roles of clathrin in the immunological synapse.

"Using state of the art microscopy tools, including the eTIRF-SIM that was custom built at the Kennedy Institute, we have found that clathrin is a common scaffold for pushing messages from T cells onto antigen presenting cells (APCs), and pulling messages into the T cells from the APCs," said Audun. "Messages in the form of vesicles are pushed directly from the plasma membrane of T cells through a process we termed clathrin- and ESCRT-mediated ectocytosis (CEME), while T cells pulling vesicles from the APCs is based on the process of clathrin-mediated endocytosis (CME). The choice of which direction the vesicles move is controlled by different adaptors, called HRS and EPN1, respectively."

The immunological synapse is the crossroads of the adaptive immune system, through which helper T cells instruct B cells to induce antibody production or killer T cells latch onto infected and cancerous cells to eradicate them.

Read the full article on the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences website

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