Antigen recognition by T cells via the T cell receptor (TCR), responsible for eradication of cancerous and virally infected cells as well as autoimmune responses and organ rejection, remains poorly understood. This is primarily due to difficulties in producing pure TCR protein, coupled with low affinity for and low expression levels of cognate pMHC.

 

By optimizing multiple aspects of recombinant expression, we were able to solve the three-dimensional structure of the first auto-immune TCR-pMHC complex, providing insight into aberrant immune recognition. This work now primarily focuses around developing a platform technology to identify TCRs with selective, low affinity for binding partners. As indicated by the successes of pMHC multimers and antibodies, such molecules could directly impact our understanding of TCR-pMHC recognition in disease (autoimmunity) and health (vaccine responses) as well as form the basis of novel reagents for immunology research and targeted immunotherapeutics.