When immune cells detect harmful pathogens or cancer, they mobilize and coordinate a competent protective response. In order to do this effectively, the immune cells must communicate in a manner consistent with the pathogenic insult. Therefore, the body's response to various health challenges depends on the successful coordination between cells of the immune system.
Major players in the immune system include helper T cells and antigen presenting cells, such as dendritic cells and B producing antibody. T cells communicate with antigen presenting cells through short-term contacts called immune synapses. These contacts are highly specialized donor cells with an appropriate platform for timely and effective exchange of information. Key messages are sent through the immune synapse via nanometer-sized vesicles called synaptic ectosomes.
A study led by the group of Professor Mike Dustin of the Kennedy Institute of Rheumatology at the University of Oxford, traces the movement of ectosomes and decomposes their contents, As described in their research results published in eLIFE, the team developed three-dimensional three-dimensional cell and successfully intercepts and decrypts messages contained in ectosomes derived from helper T cells. Using super-resolution microscopy called dSTORM, this work found that these T-cell synaptic ectosomes have scales of one millionth of a meter, but despite their reduced size, they can pack enough information to organize the response of dendritic cells . In addition, cell-free ectosomes and their synthetically developed versions lead to the maturation of dendritic cells, an essential process for establishing adequate immune responses.
Experiments with dSTORM further highlight how both antigen recognition and effector functions can coalesce into single ectosomes, suggesting that this T cell-mediated assistance is highly targeted. Finally, using mass spectrometry and CRISPR-Cas9 gene editing technology, the team further clarified key molecular machines known as ESCRT proteins responsible for sending ectosomes from helper T cells.
"This study revealed that the formation and composition of these ectosomes is dependent on direct molecular interactions at the immune synapse and has a profound impact on the understanding of cell-to-cell communication," study co-author Dr. David Saliba said. The use of this new knowledge is important for the development of future therapies that can help to shape the immune response to specific diseases.
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David G Saliba et al, Composition and structure of synaptic ectosomes carrying an antigenic receptor coupled to a functional CD40 ligand by helper T cells, eLife (201
Synthetic cells capture and reveal hidden messages of the immune system (2019, September 17)
retrieved September 17, 2019
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