Professor Andy Sewell
αβT-cells orchestrate immunity and protect against pathogens and cellular malignancies by recognising short ‘foreign’ peptides bound to major histocompatibility complex (MHC) molecules. The antigen specificity of T-cells is conferred by the highly variable complementarity determining regions (CDRs) of the αβT cell receptor (TCR) that interact with the peptide-binding platform of the MHC. T-cells are some of the most important cells in our bodies as they:
- Orchestrate immunity and are key elements in the control of infection
- Are important for the natural eradication of cancer
- Hold the key to successful vaccination
- Are an important factor in transplant rejection
- Cause all autoimmune diseases
- Mediate many allergic reactions
Thus the interaction between αβTCR and peptide-MHC (pMHC) is one of the most important interactions in biomedicine and is pivotal in many human diseases.
There are two main subtypes of αβT-cell: cytotoxic T lymphocytes (CTL) which recognise peptides in the context of MHC class I (pMHCI) and helper T-cells (Th cells) which recognise peptides in the context of MHC class II (pMHCII). Our work focuses on human T-cell antigens and the receptors that recognize them. We thus have an interest in:
- pMHCI
- pMHCII
- αβTCR (binding to pMHCI and II)
- CD4 coreceptor (binding to pMHCII)
- CD8 coreceptor (binding to pMHCI)
- γδTCR and its ligand
We are currently modifying these interactions with an aim to learn more about how T-cells function and to utilize these molecules in a therapeutic setting.