While immunotherapy has been a huge step forward in the treatment of some cancers and autoimmune diseases, there are many patients for whom this type of therapy does not work.
Australian researchers from Monash University, La Trobe University and QUT have discovered a way to “rev up” T cells, potentially increasing the scope and success of T cell-based immunotherapy.
The research, published in Nature Communications and led by Dr Pirooz Zareie and Professor Nicole La Gruta from Monash University , Dr Chris Szeto and Professor Stephanie Gras from La Trobe University and Dr Stephen Daley from QUT , identifies a new mechanism by which T cells can react to lower doses of antigens.
The research group discovered a previously unobserved immune interaction, “which had remained invisible because the level of T cell activation was above a threshold that generally results in those T cells being ‘deleted’ from the immune system,” Dr Zareie said.
The researchers found a novel biochemical mechanism by which T cells are ‘deleted’ before they can fully mature.
“We performed comprehensive biochemical affinity-based measurements and observed the formation of a covalent bond between antigens and T cell antigen receptors” said Dr Szeto. In collaboration with the Australian Synchrotron, “we confirmed the presence of a disulphide bond using X-ray crystallography” Professor Gras said.
“We provide functional evidence that this covalent interaction results in a 50-fold increase in T cell activation sensitivity” Dr Zareie added.
“This discovery came from basic research on the thymus, which is an organ that tailors the immune system to fit its host. Immunotherapy was not on our radar when we started this work, but now we can see how this natural mechanism might be co-opted in future treatments for cancer and autoimmune disease” Dr Daley noted.
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About the Monash Biomedicine Discovery Institute at Monash University
Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
About the La Trobe Institute for Molecular Science at La Trobe University
The La Trobe Institute for Molecular Science (LIMS) is dedicated to delivering translatable molecular discoveries at the interface of health and science. By bringing together La Trobe University’s leading researchers we support a cross-discipline collaborative culture and state-of-the-art research facilities. Scientists from diverse disciplines work together to achieve remarkable outcomes that would not be possible in traditional academic settings. Our high impact research generates collaborations and partnerships within Australia and internationally.
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Nature Communications
Experimental study
Cells
Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus
24-Aug-2022
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