Technology

Technology to study the TCR and CD8 co-receptor

For any advice or help on the technological approaches described here then please contact Professor Linda Wooldridge (linda.wooldridge@bristol.ac.uk) who would be happy to help!

One: pMHCI tetramer technology

Flow cytometry with fluorochrome-conjugated peptide-major histocompatibility complex (pMHC) tetramers has transformed the study of antigen-specific T-cells by enabling their visualization, enumeration, phenotypic characterization and isolation from ex vivo samples. Our interests include:

  • Improving the physical detection of T cells with low affinity TCR/pMHCI interactions typical of those that predominate in tumour-specific responses and autoimmune conditions using strategies such as dasatinib treatment.
  • Use of pMHCI tetramers to study TCR/pMHCI kinetics at the cell surface or the role that CD8 plays in CD8+ T cell activation.

Two: Quantification of TCR promiscuity

Despite the fact that TCR promiscuity has been heavily implicated in disease pathogenesis, CD8+ T cell promiscuity had never been quantified. In collaboration with Dr Hugo van den Berg, we have developed an approach to quantify TCR promiscuity. This will allow the study of promiscuity in different disease setting and help us to answer some fundamental questions.

Three: Identification of ligands that drive pathogenic TCRs

We are currently developing an approach to identify the biological ligands that drive the expansion of pathogenic CD8+ T cells in autoimmune disease, T cell leukaemia and transplant rejection with the expertise of Dr Hugo van den Berg and Dr Barbara Szomolay.