T-cell receptor on PLP178-191-specific CD4+ T cell (TCR (PLP178-191))

The T-cell receptor (TCR) on PLP178-191-specific CD4+ T cells is a molecular complex that mediates the recognition of a specific myelin proteolipid protein (PLP) epitope by the adaptive immune system. This epitope, comprising amino acids 178-191 (NTWTTCQSIAFPSK), is highly encephalitogenic and serves as a primary target for pathogenic T cells in the SJL/J mouse model of Multiple Sclerosis (MS), known as Experimental Autoimmune Encephalomyelitis (EAE) (Greer et al., 1992, J Immunol). In the context of disease, the interaction between these TCRs and the PLP178-191 peptide presented by MHC class II molecules leads to the activation of Th1 and Th17 cells, which orchestrate the inflammatory attack on the myelin sheath in the central nervous system (Waldner et al., 2000, J Clin Invest). Because of its central role in driving autoimmune pathology, this TCR is a key target for antigen-specific immunotherapies designed to induce immune tolerance. Experimental treatments include altered peptide ligands (APLs), peptide-coupled nanoparticles, and soluble MHC-peptide multimers, which aim to either delete the autoreactive T cells, induce anergy, or promote the differentiation of regulatory T cells (Tregs) (Miller et al., 2007, Nat Rev Immunol). Successfully modulating these specific TCR-mediated responses offers the potential to treat MS without the side effects associated with systemic immunosuppression. Monitoring the activity and frequency of these specific T cells via MHC-peptide tetramers serves as a critical biomarker for evaluating the efficacy of such immunotherapies.

Other names

PLP178-191-specific T-cell receptorMyelin proteolipid protein 178-191-specific TCRTCR on PLP-reactive CD4+ T cellsPLP178-191-specific TCR

Induction of antigen-specific immune tolerance through T-cell anergy, clonal deletion, or the expansion of regulatory T cells (Tregs) by targeting the TCR-MHC-peptide interaction.