Autoimmune diseases are chronic disorders that develop due to the breakdown of immune tolerance towards self-antigens triggered by environmental factors in genetic predisposed individuals. Research in both humans and animal models has identified abnormal humoral and cellular immune responses against self-protein antigens as key mechanisms driving these diseases. However, despite significant research efforts, understanding the cellular and molecular players involved in the immunopathology of human autoimmune diseases remains a major medical challenge.

Multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS), is characterised by demyelination and neuronal loss, along with immune cell brain infiltration and inflammation. While the contribution of autoreactive T cell immunity targeting CNS protein antigens to MS immunopathology is well recognized, the precise immune-mediated mechanisms are still not fully understood. Increasing evidence suggests that T cells recognizing self-lipids presented by group 1 CD1 molecules may also play a harmful role in human autoimmunity. However, this aspect has been largely overlooked due to the absence of group 1 CD1 molecules in mice and the lack of sensitive technologies to detect, isolate, and characterise potentially rare lipid-reactive human T cells.

Hosted at OSR, this project aims to establish new experimental approaches and investigate the potential existence and immunological role of T cells recognizing self-lipids in MS. We aim to provide the first systematic analysis of self-lipid reactive T cells in health and disease settings. The overarching goal is to define signatures that may help stratify MS patients and healthy conditions and given the monomorphic nature of CD1 molecules, potentially lead to a universal treatment.