“We were able to precisely visualise how the nanobody simultaneously recognised CD1d and the NKT TCR, thereby providing a molecular basis for their anti-tumour properties.”
As well as T cells sensing peptides presented by MHC molecules (Theme 5), they can also respond to lipids (this theme) and metabolites (Theme 7). In the context of lipid-mediated immunity, TCRs recognise lipids that are presented by MHC-I like molecules, namely the CD1 family.
PROF. JAMIE ROSSJOHN
PROF. DALE GODFREY
AT A GLANCE
There are four members of the CD1 family of antigen-presenting molecules expressed on the cell surace (CD1a,b,c,d), each of which possesses unique structural and biochemical/cellular features that indicates distinct roles in immunity. Indeed, it is now becoming evident – in part due to the contributions of Imaging CoE scientists – that the CD1 family can play an important role in both protective immunity (e.g. response to Mycobaterium tuberculosis) and immunopathology. Imaging CoE scientists continue to pioneer this aspect of immunity.
Our findings in this area have led to:
- Characterisation of potent anti-tumour responses by single-domain antibodies targeting the CD1d-NKT axis (Lameris, et al., Nature Cancer 2020).
- Mechanisms of γδ T cell recognition of CD1b (Reijneveld, et al., PNAS 2020).
- Identification of human skin T cells that recognise CD1a independent of lipid (Cotton, et al., Journal of Clinical Investigation 2021).
- Glycolipid-peptide vaccination protects against rodent malaria via liver-resident CD8+ T cells (Holz, et al., Science Immunology 2020).
- Identification of the CD36 lipid scavenger molecules as non-TCR ligands for CD1 family members (Gherardin et al. BioRXiv 2021).
- Identification of a population of T cells that can recognise self-lipid antigens in conjunction with sulfa drug-like molecules presented by CD1d (Almeida et al. BioRXiv 2021).
- Explored the range of lipid antigens presented by CD1 and the ensuing immune response.
- Expanded our understanding of the αβ and γδ T cell repertoire reactive towards CD1.
- Characterised novel therapy targets that act via the CD1 axis.