Harnessing CD4+ T cell effectors for lymphoma therapy

Preece, Shân (2018). Harnessing CD4+ T cell effectors for lymphoma therapy. University of Birmingham. M.Sc.

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Abstract

CD4+ T cells play a pivotal role in orchestrating immune responses. It has now been shown that some cells display direct effector functioning in the elimination of viral infections and cancers. The T cell receptor (TCR) is thought to play a part in influencing these cytotoxic mechanisms and is being investigated for optimisation of TCR gene transfer therapies. However, with the diverse TCR repertoire available, selection of TCRs conferring the greatest therapeutic potential remains a challenge.

To investigate TCRv~ usage and its effects on cellular function, in the context of the oncogenetic Epstein Barr Virus, we used MHC class II tetramers to isolate CD4+ T cell clones from healthy seropositive donor's ex vivo, specific for the latency ill EBNA2 protein derived epitope; PRS.

We have found that the epitope specific CD4+ T cells express TCRs with various v~ usages. These T cells had a range of functional avidities for the same MHCII-epitope combination. We have further shown there is a direct relationship between functional avidity and the efficiency of a T cell clone to recognise unmanipulated LCL targets (EBV infected B cells).

The results from these experiments highlight the importance of gaining further knowledge into the relationship between TCR usage and T cell function. This may provide steps towards future development of targeted MHC Class II restricted TCR gene transfer therapies for the treatment of EBV associated B cell malignancies.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):