Myelin basic protein 83-99-specific T-cell receptor (MBP83-99-specific TCR)

The Myelin basic protein 83-99-specific T-cell receptor is a specialized immune receptor that plays a central role in the pathogenesis of Multiple Sclerosis (MS) (Wucherpfennig et al., 1994). It specifically recognizes the immunodominant 83-99 peptide fragment of Myelin Basic Protein (MBP) when presented by the MHC class II molecule HLA-DR2, specifically the HLA-DRB1*15:01 allele (Hahn et al., 2005). This recognition forms a trimolecular complex (TCR–MBP–MHC) that triggers the activation and proliferation of autoreactive CD4+ T cells (Bielekova et al., 2000). These activated T cells cross the blood-brain barrier and initiate the inflammatory destruction of the myelin sheath in the central nervous system (Kim et al., 2021). Because this interaction is a primary driver of neuroinflammation, it is a major target for antigen-specific immunotherapies (Steinman, 2004). Therapeutic strategies include the use of altered peptide ligands (APLs) and tolerogenic vaccines designed to modulate the TCR signal to induce immune tolerance or shift the T-cell phenotype from pro-inflammatory to regulatory (Kim et al., 2021). However, targeting this complex is challenging due to the historical risk of inducing anaphylaxis or inadvertently worsening the autoimmune response through partial agonism (Bielekova et al., 2000).

Other names

MBP-specific TCRMyelin basic protein (83-99)-reactive T-cell receptorHLA-DR2-restricted MBP-specific TCRAnti-MBP TCRTCR-MBP-MHC trimolecular complex

Induction of immune tolerance through altered peptide ligand signaling, competitive inhibition of antigen presentation at the MHC interface, or induction of T-cell anergy and exhaustion.