BBSRC MATSYB network  I2M: Immunology, Imaging and Modelling

second meeting of the network: 21 May 2008

Institute of Child Health, University College London.



  • Location

    Room A, Wellcome Trust Building


    How to get to Institute of Child Health


  • 10:00-10:45  

    Hugo van den Berg


    Dynamic TCR crossreactivity through coreceptor tuning

    The functional sensitivity of a T cell to peptide-MHC ligands is a dynamic quantity which is continually being adjusted by immunoregulatory mechanisms. This process is vital in the maintenance of a diverse repertoire, avoidance of autoimmunity, and the ability to mount an efficacious immune response against a pathogenic challenge. There are various modulatory mechanisms which, acting in concert, alter a T cell's activation threshold through costimulation and its TCR's affinity and triggering threshold through coreceptor tuning. Various mechanism have been proposed for the effect of the coreceptor CD8 on TCR sensitivity. We have studied the quantitative importance of each mechanism, combining experiments and theoretical analysis. These studies suggest that the TCR repertoire resolves the paradox of attaining sufficient functional diversity with a comparatively modest number of clonotypes, whilst avoiding autoimmunity, by means of a novel mechanism which we call "focussed specificity". On this theory, each TCR is potentially crossreactive to many ligands, but will at any one time have a large functional sensitivity to only a few of them. Dynamic specifity focussing would constitute the T cell counterpart to affinity maturation in B cell immunity.
  • 11:00-11:45  

    Graham Anderson

    MRC Centre for Immune Regulation, University of Birmingham, B15 2TT

    Regulation of T-cell Development In The Thymus

    The development of functionally competent antigen-specific T-cells occurs within the thymus. Blood-borne immature T-cell progenitors are recruited to the thymus by a chemotactic process, involving CCR7- CCL21 and CCR9-CCL25 interactions. Development of T-cell progenitors within the thymus involves a complex series of steps including proliferation, antigen receptor gene rearrangement, differentiation, and selection of T-cell receptor specificities to ensure the production of a self-tolerant T-cell repertoire. It is clear that all the appropriate queues that drive T-cell development are provided by stromal cells that make up the thymic microenvironment. These cells include cortical and medullary epithelial cells, dendritic cells, macrophages and mesenchymal fibroblasts. To gain a better understanding of how thymic stromal cells regulate T-cell development, we have established in vitro techniques based on the disaggregation and reaggregation of thymic tissue. This allows us to form three-dimensional thymic structures in vitro from defined thymocyte and stromal cell subsets, enabling the analysis of specific developmental events in a synchronous fashion. Data presented will summarise our use of this system to study the positive and negative selection of the T-cell repertoire, as well as the processes driving thymic epithelial cell development.
  • 11:45-12:30 discussion
  • 12:30-2:00 lunch
  • 2:00-2:45

    Rachel Norman

    Head of the Mathematics and Statistics Group Department of Computing Science and Mathematics University of Stirling

    Mathematical Models of Disease Systems: an Applied Example and a Theoretical Approach.

    The talk will consist of two parts. In the first I will present work which has been carried out for a number of years on modelling Louping ill virus. This is a tick borne infection of sheep and grouse which is of economic importance in the Scottish Highlands. There are a number of different hosts involved in this system, some which are simply hosts for the ticks (e.g. deer) and some which are involved in disease transmission (e.g. mountain hares). In this part of the talk we will look how we might control the disease by manipulating the host densities on different estates. In the second part of the talk I will introduce a new theoretical approach which I have been working on with colleagues in Computing Science. We have utilised a technique which allows us to write down rules of individual behaviour and then to scale up to behaviour at the population level. I will illustrate this by looking at transmission in a disease system, but this could easily be applied to a number of different systems, including immunological ones.
  • 3:00-4:30 discussion (proposals, FP7, web of network, INI programme, etc.)

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