Fabien Garcon is available for consultancy.
Activation of T lymphocytes by recognition of a peptide/MCH at the surface of an antigen presenting cell (APC) requires the formation of a tight contact between the two cells, during which T cells undergo dramatic morphological changes. Maintenance of a stabilised interaction is correlated with full T cell activation. One of the earliest biochemical signals observed after T cell contacted an APC is the generation of PI(3,4,5)P3, products of the PI3-kinase (PI3K) activity. In many cell systems, PI3K is known to contribute to several aspects of cell polarisation and migration.
The purpose of my work is to understand why PI3K-deficient T cells are defective in forming conjugates with antigen presenting cells and how this impacts on T cell function in PI3K deficient mice.
helper T cells ; PI3K ; calcium imaging ; T cells ; confocal microscopy ; FACS ; signalling ; T cell receptor (TCR) ; immunological synapse
Soond DR, Garçon F, Patton DT, Rolf J, Turner M, Scudamore C, Garden OA, Okkenhaug K. Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma. J Immunol. 2012 Jun 15;188(12):5935-43.
Ramadani F, Bolland DJ, Garcon F, Emery JL, Vanhaesebroeck B, Corcoran AE, Okkenhaug K. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci Signal. 2010 Aug 10;3(134)
Saudemont A, Garçon F, Yadi H, Roche-Molina M, Kim N, Segonds-Pichon A, Martín-Fontecha A, Okkenhaug K, Colucci F. p110gamma and p110delta isoforms of phosphoinositide 3-kinase differentially regulate natural killer cell migration in health and disease. Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5795-800.
Garcon F, Patton PT, Emery JL, Hirsch E, Rottapel R, Sasaki T, Okkenhaug K, CD28 provides T cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer, Blood 2008 111:1464–1471
Patton DT, Garçon F, Okkenhaug K, The PI3K p110delta controls T-cell development, differentiation and function, Biochemical Society Transactions 2007 35:167–171
Okkenhaug K, Patton DT, Bilancio A, Garçon F, Rowan W, Vanhaesebroeck B,The p110delta isoform of phosphoinositide 3-Kinase controls clonal expansion and differentiation of T cells, Journal of Immunology 2006 177:5122–5128