This latest study, funded by The Wellcome Trust, is the first to compare the two main methods used to study the signalling pathways of these genes as well as analysing them to better understand what types of TCR signals they may sense. The first and perhaps the most established in the field uses a genetically engineered mouse model ‘Nr4a1-GFP’ which makes green fluorescent protein in cells that are expressing the gene Nr4a1. The second, co-invented by Dr David Bending at the University of Birmingham’s Institute of Immunology and Immunotherapy is a novel technology using Nr4a3-Tocky mice which make a fluorescent protein that changes colour over time in response to TCR signals.
The study has revealed crucial differences between the technologies which could make them complimentary in studying different types of TCR signals. For example, the Nr4a1-GFP system is very sensitive to TCR signals, and therefore has the ability to capture the very short signals received by T cells that help them develop and survive. On the other hand, the Nr4a3-Tocky system requires longer TCR signals, which are generally seen only during immune responses. The findings were particularly interesting as Nr4a1 and Nr4a3 genes are from the same gene family and share significant similarities in their genetic codes however, as this study has shown, they are controlled by different signalling pathways.