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. In the recently published work in PNAS, Audun Kvalvaag and colleagues describe how direct two-way communication between T cells and antigen-presenting cells (APCs) at the immunological synapse is regulated. The work started with 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 help generate small packages of information that can be released from cells called exosomes.
" Using state of the art microscopy tools, we have found that clathrin is a common scaffold for pushing messages from T cells onto 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 adapters, called HRS and Epsin-1, respectively. "
This novel understanding of how communication between T cells and APCs is regulated might open new avenues for therapeutic intervention in cancer and infectious disease.
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