Investigating the control of CD8 T cell response diversity

Project Overview

We are interested in understanding how cells of the adaptive immune system, in particular CD8 T cells, are recruited and organised in space and time in vivo during vaccination and infections (1,2). CD8 T cell responses are composed of multiple clones recognizing their activating peptide with different affinities. This clonally diverse response is consistently observed, and interestingly, does not lead to autoimmunity. Our group is studying multiple parameters controlling the breadth of this diversity. We recently discovered that CD8 T cells interact with each other, forming T cell–T cell synapses required for their differentiation (1,3). This project will investigate how CD8 T cells use this direct way of communicating to control which clones are recruited to a response. We will analyse how multiple CD8 T cell clones are organized relative to each other in space and time. We will also incorporate functional reporters and knockout technology to evaluate communication and better elucidate how this dynamic shapes the efficiency and fate of their response. This project involves 2-photon microscopy, immunological assays and TCR sequencing. These studies will identify mechanisms used by CD8 T cells to self-control their response to ultimately maintain the balance between immunity and tolerance.

Training Opportunities

The Kennedy Institute is a world-renowned research centre and is housed in a brand new state-of-the-art research facility. Full training will be provided in a range of cell and molecular biology techniques, and imaging. A core curriculum of 20 lectures will be taken in the first term of year 1 to provide a solid foundation in immunology and data analysis. Students will attend weekly departmental meetings and will be expected to attend seminars within the department and those relevant in the wider University. Students will also attend external scientific conferences where they will be expected to present the research findings.

Relevant Publications

1. Secondary T cell-T cell synaptic interactions drive the differentiation of protective CD8+ T cells. Gérard A. et al, (2013), Nat Immunol, 14, 356 – 363.
2. Detection of rare antigen-presenting cells through T cell-intrinsic meandering motility, mediated by Myo1g. Gérard A. et al, (2014), Cell, 158, 492 – 505.
3. Evolving immune circuits are generated by flexible, motile, and sequential immunological synapses. Gérard A. et al, (2013), Immunol Rev, 251, 80 - 96.

Scientific Themes

Immunology; Adaptive immunity

Further information

Dr Audrey Gérard, Kennedy Institute, University of Oxford
audrey.gerard@kennedy.ox.ac.uk