T-cell receptor on Myelin oligodendrocyte glycoprotein 35-55-specific CD4+ T cells (TCR (MOG35-55))

The T-cell receptor (TCR) on MOG35-55-specific CD4+ T cells is a specialized protein complex that plays a pivotal role in the pathogenesis of neuroinflammatory diseases like Multiple Sclerosis (MS) and its primary animal model, Experimental Autoimmune Encephalomyelitis (EAE) (Bittner et al., 2014). This receptor specifically recognizes the immunodominant 35-55 peptide fragment of Myelin Oligodendrocyte Glycoprotein (MOG) when it is presented by Major Histocompatibility Complex (MHC) class II molecules, such as HLA-DR2 in humans or I-Ab in mice (Burrows et al., 1999). In the context of autoimmunity, the activation of these T cells via their TCR triggers a cascade of pro-inflammatory events, including the secretion of cytokines such as IFN-gamma, IL-17, and GM-CSF (Rodi et al., 2024). These events lead to the infiltration of the central nervous system by immune cells, resulting in the destruction of the myelin sheath and subsequent axonal damage (Galicia et al., 2013). Because this TCR is the primary driver of the antigen-specific autoimmune response, it is a major target for therapeutic intervention aimed at restoring immune tolerance (Yadav et al., 2021). Experimental drugs like RTL1000, a recombinant T-cell receptor ligand, and various tolerogenic vaccines like OM-MOG35-55 or GMCSF-MOG aim to interact with this receptor to suppress pathogenic responses (Offner et al., 2011). These therapies work by promoting the development of regulatory T cells (Tregs) or by inducing anergy or apoptosis in the autoreactive T-cell population (Mannie et al., 2011). By specifically targeting the MOG35-55-specific TCR, these approaches seek to halt the progression of demyelinating disease without the broad side effects associated with systemic immunosuppression (Rodi et al., 2024).

Other names

MOG-specific T-cell receptorMyelin oligodendrocyte glycoprotein 35-55-specific T-cell receptor2D2 T-cell receptorMOG35-55-specific TCRT-cell receptor on MOG35-55-specific CD4+ T cells

Induction of antigen-specific immune tolerance through the interaction with the T-cell receptor, leading to the suppression of pathogenic Th1 and Th17 responses, induction of regulatory T cells (Tregs), or deletion of autoreactive T cells.