T-Cell Antigen Specificity Group
T Cell Receptors (TCRs) play a pivotal role in orchestrating cellular immunity in health and disease. The underpinning rules of T cell recognition of target antigens are incompletely understood. In fact, in silico reconstruction of map between TCRs and their cognate targets remains as a holy grail of modern systems immunology. We therefore try to decode the principles of antigen-specific T cell response in time and space.
Research
The primary objective of research in our group is to combine advanced machine learning and computational techniques with state-of-the-art multimodal single cell experimental technologies to investigate the development, regulation, and variability of the adaptive immune response in both health and disease. Our focus includes dynamics of the adaptive immune response to pathogens, autoimmunity, cancer, and vaccination at both cellular and tissue level.
T cell immunity, specifically the computational inference of T cell antigen specificity, is a critical aspect of modern systems immunology, and remains as a challenge to researchers in the field (Nat.Rev.Imm). Upon joining Oxford University, I established a research programme aimed at contributing to this complex and significant problem. Upon sudden emergence of SARS-CoV-2, I tried to translate the devastation of the pandemic into an opportunity. As such, I adapted the skills and resources in my group, and led a series of studies to further our understanding of the mechanism behind the heterogeneity of the immune response to natural infection and vaccination.
This started by in silico prediction of parts the virus genome which are more likely to be recognized by T cells (F1000Reseach 2020). We then investigated the extent of T-cell cross-immunity in driving the variable outcome of the disease (Frontiers in Immunology 2020), that was followed by investigating the genetic basis of T cell cross-immunity among the population (Immunology 2022).
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