Gérard Group | Spatiotemporal dynamics of T cell responses
We are interested in understanding how recruitment and differentiation of different CD8 T cell clones are organised in space and time to achieve the correct balance between tolerance and immunity.
How cells collectively maintain the integrity of an organ, system or organism is a fundamental question in biology. This has been particularly elusive in the context of the immune system where the cell types and signals involved are dynamic and widely spread throughout the body.
We are interested in understanding the collective response of CD8 T cells. Each CD8 T cell clone expresses a specific T cell receptor with unique antigen specificity. During infection, the response of individual T cell clones averages to produce a consistent response. We investigate how the recruitment and differentiation of different T cell clones and subsets is organised in space and time to achieve the correct balance between tolerance and immunity. The lab has two main focuses:
1. CD8 T cell collective-decision making during the initiation of immune responses.
We are interested in the cellular communications that regulate the collective behaviour of CD8 T cells. We previously discovered that CD8 T cells interact with each other, forming T cell–T cell synapses required for their differentiation (Gérard et al, Nature Immunology 2013). We are now investigating how direct communication between CD8 T cells shapes the breadth of a T cell responses and which signals are involved. To address this question, we use a combination of imaging, functional assays and genomics.
2. Migration patterns and clonal breadth of T cell responses.
Our lab addresses the relationship between cellular migration patterns and the recruitment of diverse T cell clones and subsets into a response. We previously found that T cells display discrete migration patterns allowing for both exploration of a large territory and efficient scanning of potential antigen-presenting cells (APCs). These migration patterns are required for eradication of infectious agents such as Listeria (Gérard et al, Cell 2014). We are now investigating whether T cell migration patterns are optimized to maximally recruit all cognate T cells to a response. To address this question, we use micro-fabricated devices and in vivo imaging, and combine empirical data with simulation.