The role of Caveolin-1 in regulating primary T cell responses

Lead Research Organisation: University of Edinburgh
Department Name: Edinburgh Research and Innovation


T cells are cells of the immune system that are very important in protecting us against infection by viruses, bacteria and other disease causing organisms (pathogens). The cells get activated when the body is infected and divide so that they can mount an immune response to eliminate the pathogen. Once the pathogen is gone, the excess pathogen-specific cells die off and the remainder revert to a resting state ready for a subsequent infection with the same pathogen. Occasionally the cells fail to die off and/or fail to rest in which case inflammation and autoimmunity may result. We are trying to understand at the molecular level how the cells move from resting to activated state and back again. A molecule called Caveolin 1 has been shown regulate activation, growth and division of skin cells and endothelial cells and we have recently found this molecule is expressed in T cells. Our research asks how Caveolin influences the activation and regulation of T cells so that we can better understand these processes. With this knowledge we can devise strategies for influencing T cell activation which has impact for vaccination strategies and the control of autoimmune disease.

Technical Summary

The question of how T cell activation is controlled is fundamental to understanding how adaptive immune responses are regulated. T cells are activated by engaging cell surface receptors which link to multiple intracellular signalling pathways. Intracellular signalling needs to be co-ordinated in space and time so that proliferation and differentiation of T cells are both initiated and terminated appropriately. Failure to do so can lead to uncontrolled T cell expansion and potentially lethal inflammatory sequelae. We report, for the first time, expression in T cells of a molecule, Caveolin 1 (Cav1), known to be important for co-ordination of signal transduction pathways in many cell types. Cav1 is involved in regulation of inflammation and anchorage dependent growth control in endothelial and epithelial cells through its interaction with key signal transduction proteins such as: G protein a subunits, eNOS, EGF-R, PKCa, Integrins and Src-family kinases. We present preliminary data showing that Cav1 is involved in T cell receptor signalling and is phosphorylated in responce to T cell receptor engagement. We propose to further characterise its role in regulating T cell responses. These studies will tell us whether the function of Cav1 and phospho-Cav1 in T cells is the same as that described for adherent cells, which will enhance our knowledge about both Cav1 function and T cell biology. Alternatively there may be aspects of Cav1 function that are unique to T cells which will provide novel insights into the regulation of T cell activation and signalling.


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