Molecular mimicry as a key parameter shaping T cell immunitycore
MIMIC · Horizon Europe grant · 2022-09-01–2027-08-31
EC contribution
Total cost
Beneficiaries
About the data
Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call ERC-2021-COG · scheme HORIZON-ERC · topic ERC-2021-COG. CORDIS record →
Objective
Scientific Challenge: Immunotherapy has revolutionized cancer treatment, yet only a minor fraction of patients respond to frequently used immunotherapeutic treatments. T cell recognition of peptide-major histocompatibility (pMHC) class I complexes is essential to maintain immune surveillance and eliminate cancerous cells. Numerous products of genetic and epigenetic alterations can serve as targets for T cell recognition of cancer, yet our capacity to predict what MHC-embedded targets T cells can recognize on the surface of cancer cells is still poor, with a less than 5% hit rate. While we have robust tools for prediction of antigen presentation, we still have very limited understanding of the factors driving immunogenicity – i.e. which of the presented targets will give rise to a T cell recognition. A fundamental mechanism influencing T cell recognition is molecular mimicry. It has long been proposed that the ability of a given T-cell receptor (TCR) to recognize multiple different pMHC complexes is essential to provide immunological coverage of all potential pathogens that we may encounter. T cell epitopes, that at first glance appear very different, may have structural similarities once embedded in the MHC I binding groove, and hence appear similar to the given TCR (molecular mimicry).Objective: In MIMIC, I will determine the role of molecular mimicry in T cell recognition and demonstrate how pre-existing immunity may shape the T cell recognition of cancer antigens. I will use the SARS-CoV2 infection as a model system to understand molecular mimicry, and apply the learnings from this to cancer immunogenicity. Expected outcome: I predict that by understanding the influence of molecular mimicry, the rules governing the immunogenicity of T cell epitopes can be determined and the selection of antigens optimized - this will be essential to develop precision T cell therapies targeting tumor antigens of relevance for the individual patient.
Beneficiaries (1)
| Organisation | Country | Role | EC contribution | SME |
|---|---|---|---|---|
| DANMARKS TEKNISKE UNIVERSITET | DK | coordinator | €2,000,000 |
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