The influence of proximal TCR signalling molecules in controlling T cell activation

Friday 10 November 2017, 1.00PM

Speaker(s): Rose Zamoyska, University of Edinburgh

Engagement of T cell receptors (TCRs) on naïve T cells by peptide:MHC ligands leads to a variety of outcomes depending on the affinity and dwell time of the interaction. Weak interactions, such as through self-peptide:MHC, deliver survival signals to T cells but do not normally induce proliferation and differentiation, unless under conditions of lymphopenia or inflammation. In contrast, strong interactions lead to metabolic changes, proliferation and development of effector function. We have been investigating the impact of proximal kinases and phosphatases on CD8 T cell receptor ligand discrimination and the subsequent T cell response. For example, loss of the key tyrosine kinase Lck compromises multiple signalling pathways and leads to insufficient production of ribosomes upon stimulation and a failure to sustain proliferation. A similar effect is observed upon stimulation of naïve CD8 T cells with weak altered peptide ligands. In contrast, loss of the phosphatase PTPN22, a negative regulator of Lck activity, increases TCR sensitivity, in particular to weak ligands, and enhances proliferation and effector function. These data will be discussed in respect of how T cell signalling may be manipulated in pathogenic situations such as autoimmunity and tumour immunotherapy.

The host for this seminar is James Hewitson 

Location: K018


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