T-cell receptor recognizing myelin peptide–MHC II complexes (Myelin-specific TCR)

The T-cell receptor (TCR) recognizing myelin peptide–MHC II complexes is a specialized antigen receptor found on the surface of autoreactive CD4+ T lymphocytes (Hahn et al., 2005). In the context of Multiple Sclerosis (MS), these TCRs recognize self-antigens derived from the myelin sheath, such as Myelin Basic Protein (MBP), Myelin Oligodendrocyte Glycoprotein (MOG), and Proteolipid Protein (PLP), which are presented by Major Histocompatibility Complex class II (MHC II) molecules on antigen-presenting cells (Li et al., 2005). The engagement of the TCR with these myelin-pMHC complexes is the primary driver of the inflammatory cascade that leads to demyelination and axonal damage in the central nervous system (Yin et al., 2012). Therapeutic interventions targeting this specific interaction aim to achieve antigen-specific immunotherapy, which selectively modulates the pathogenic immune response while sparing the rest of the immune system (MDPI, 2024). Current strategies include the development of altered peptide ligands (APLs), which are modified peptides that bind the TCR with different affinity to induce anergy (Neurocrine Biosciences, 2005). Other approaches utilize soluble recombinant TCR ligands (RTLs) or nanoparticles decorated with pMHC complexes to induce tolerance or expand regulatory T cells (Artielle ImmunoTherapeutics, 2015). TCR-like antibodies are also being developed to block the recognition interface or deplete auto-antigen presenting cells (Frontiers in Immunology, 2022). Despite the high specificity of these approaches, challenges remain regarding the heterogeneity of myelin antigens and the potential for disease exacerbation if the TCR is partially agonized.

Other names

Myelin-reactive T-cell receptorMBP-specific T-cell receptorMOG-specific T-cell receptorPLP-specific T-cell receptorAutoreactive T-cell receptorMyelin-pMHC-specific TCR

Antigen-specific immune tolerance induction through competitive inhibition of TCR-pMHC binding, induction of T-cell anergy or deletion, and expansion of antigen-specific regulatory T cells.