PI3K signalling at the immune synapse, asymmetric division and immunoligical memory

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED


Antigens are molecules that are recognised by the immune system. Antigen presenting cells are specialised in devouring foreign particles, digesting them in to smaller fragments, and presenting these fragments to the T cells (a type of white blood cell). The T cells respond by stimulating other cells of the immune response to secrete antibodies that eliminate the pathogen. Cytotoxic T cells act by killing infected host cells, thus incapacitating the pathogen inside. Both these T cell types will be investigated as part of this proposal. P110delta belongs to a family of enzymes called phosphoinositide 3-kinases (PI3Ks for short). We have engineered mice in which the gene for p110delta is modified such that the enzyme is no longer functional. T cells from such mice are poor at forming conjugates with antigen presenting cells. Moreover, we have evidence that p110delta-deficient T cells fail to organise themselves in the right conformation to maximise their ability to read and interpret the signals provided by the antigen presenting cells. The first purpose of this grant is to more fully characterise these defects at the molecular level as it is at present not obvious why p110delta should be important for conjugate formation between immune cells. Next, we will determine how important this actually is for the ability of T cells to respond to infectious agents. We will monitor how p110?-deficiency affects T cells responses after infection with a bacterium called Listeria monocytogenes. This bacterium is sometimes found in unpasteurised milk products, such as cheese, and can cause disease and mortality in humans.


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