Unconventional aspects of MR1 restricted T-cells
Lead Research Organisation:
University of Oxford
Department Name: Clinical Medicine
Abstract
MR1-reactive T cells (MR1-T) are an abundant human subset which "bridge" between innate and adaptive immunity. These cells show enrichment in mucosal tissues and also in tumours. They are activated both through their relatively restricted T cell receptor (TCR) and specific subsets (MAIT) are highly cytokine responsive. Upon activation they are able to secrete a range of pro-inflammatory and anti-microbial cytokines, and also kill targets. Thus they are of potential interest in host defence and the therapy of cancer.
MR1-T cells are abundant in human blood include Va7.2+ MAIT, which react to microbial molecules, such as 5OPRU. There are other populations of MR-1 T cells which do not express the Va7.2 TCR and appear to respond to tumour cells. The molecular targets of these T cells are not known and their potential in control of tumours remains unclear.
This project aims to
- Generate soluble TCRs from MR1- T cells for use in detection of MR1 expressing tumour cell lines. These TCRs will be modified through mutational approaches to enhance binding and sensitivity.
- Test these TCRs as bispecific molecules in vitro to define their specificity and sensitivity
- Test these reagents using a new method (Chip Cytometry) to identify presentation of ligand in situ in cancer tissues
- Screen mucosa-derived and tumour-derived MR1-T cell clones for novel TCRs and novel reactivities.
The student will work closely with Immunocore scientists to develop and test the new tools, and with University scientists to analyse their biologic roles and activity in tissues.
Relevance: This project is aimed to address basic science questions regarding tumour immunity, and also to translate these for the improvement of human health.
Benefits for both partners: Immunocore will benefit from a close collaboration with a clinical group working in a relevant area, with well-established immunology and clinical platforms. The ability to work with material that is directly relevant to cancer and that is derived from well-defined tissue is an enormous advantage to the project and of real value to Immunocore. Technically the ability to stain soluble receptors in tissue slices using the Chip Cytometry approach is a major collaborative benefit.
The University department will benefit through collaboration with experts on T cell biology with specific expertise in MR1- T cells, which will be an important new development. We will gain expertise in the clones, new materials and specifically we will have access to novel reagents to better define the immunology of tumours at presentation and following interventions. Intellectually there is already excellent opportunity for the team members to exchange ideas about this sort of investigation and approach. Overall there is a natural fit here and major evident benefits for all concerned.
MR1-T cells are abundant in human blood include Va7.2+ MAIT, which react to microbial molecules, such as 5OPRU. There are other populations of MR-1 T cells which do not express the Va7.2 TCR and appear to respond to tumour cells. The molecular targets of these T cells are not known and their potential in control of tumours remains unclear.
This project aims to
- Generate soluble TCRs from MR1- T cells for use in detection of MR1 expressing tumour cell lines. These TCRs will be modified through mutational approaches to enhance binding and sensitivity.
- Test these TCRs as bispecific molecules in vitro to define their specificity and sensitivity
- Test these reagents using a new method (Chip Cytometry) to identify presentation of ligand in situ in cancer tissues
- Screen mucosa-derived and tumour-derived MR1-T cell clones for novel TCRs and novel reactivities.
The student will work closely with Immunocore scientists to develop and test the new tools, and with University scientists to analyse their biologic roles and activity in tissues.
Relevance: This project is aimed to address basic science questions regarding tumour immunity, and also to translate these for the improvement of human health.
Benefits for both partners: Immunocore will benefit from a close collaboration with a clinical group working in a relevant area, with well-established immunology and clinical platforms. The ability to work with material that is directly relevant to cancer and that is derived from well-defined tissue is an enormous advantage to the project and of real value to Immunocore. Technically the ability to stain soluble receptors in tissue slices using the Chip Cytometry approach is a major collaborative benefit.
The University department will benefit through collaboration with experts on T cell biology with specific expertise in MR1- T cells, which will be an important new development. We will gain expertise in the clones, new materials and specifically we will have access to novel reagents to better define the immunology of tumours at presentation and following interventions. Intellectually there is already excellent opportunity for the team members to exchange ideas about this sort of investigation and approach. Overall there is a natural fit here and major evident benefits for all concerned.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/R015708/1 | 01/10/2018 | 30/09/2025 | |||
| 2118261 | Studentship | MR/R015708/1 | 01/10/2018 | 30/09/2022 |