Mapping T cell antigen-specificity in LGI1 antibody encephalitis

Background
Autoimmune encephalitis refers to brain inflammation due to a misdirected immune response. This condition causes many symptoms including memory loss, seizures and psychiatric issues. Autoantibodies against Leucine Rich Glioma Inactivated 1 (LGI1) cause LGI1 antibody encephalitis, the commonest type of autoimmune encephalitis. Although steroids and other immune therapies are available, patients with LGI1 antibody encephalitis suffer long-term problems with mood, memory and fatigue despite current best treatments.
Although B cells produce LGI1 autoantibodies, there is strong evidence that T cells are also important in LGI1 antibody encephalitis. T cells are immune cells that use T cell receptors to recognise particular small sections of proteins called peptides and then generate an immune response either directly or through activating other immune cell types. T cells provide an effective defence against infections and tumours but can cause autoimmunity when they react to peptides naturally present in the body.
T cells develop in an organ called the thymus, in which T cells recognising self-peptides are eliminated through a process called negative selection. However, negative selection is imperfect and can result in self-reactive T cells being present in the blood and other parts of the body.
I aim to study LGI1-reactive T cells in LGI1 antibody encephalitis throughout the entire development of T cells: from their initial production in the thymus, to their initial reaction against LGI1 peptides in peripheral blood, and to their eventual inflammatory response within cerebrospinal fluid (CSF) surrounding the brain.
This project will comprehensively understand how T cells target LGI1 peptides in LGI1 antibody encephalitis, and ultimately lead to the development of new LGI1-specific T cell-targeted treatments.

Approach
I will use small peptides generated by splitting the LGI1 protein into small fragments to activate T cells from the peripheral blood of...