Myelin-derived peptide–Major Histocompatibility Complex (Myelin pMHC)

Myelin-derived peptide–Major Histocompatibility Complex (MHC) complexes are molecular structures formed on the surface of antigen-presenting cells (APCs) that play a pivotal role in the pathogenesis of Multiple Sclerosis (MS) (Nature Reviews Neurology, 2019). These complexes consist of fragments from myelin proteins, such as Myelin Basic Protein (MBP), Proteolipid Protein (PLP), or Myelin Oligodendrocyte Glycoprotein (MOG), bound to MHC Class I or II molecules (Journal of Clinical Investigation, 2015). In autoimmune conditions, these complexes are erroneously recognized by autoreactive T cells as foreign, triggering an inflammatory cascade that destroys the protective myelin sheath of neurons (PubMed, PMID: 25646831). Therapeutically, these complexes are targeted by inverse vaccines and antigen-specific immunotherapies designed to reprogram the immune system's response to self-antigens (Anokion, 2023). By presenting these myelin peptides in a non-inflammatory or tolerogenic context, such as via liver-targeted delivery or nanoparticle-mediated presentation, drugs aim to induce immune tolerance (Nature Communications, 2016). The goal of these therapies is to promote the expansion of regulatory T cells (Tregs) or to induce anergy or deletion of the pathogenic T cells (Parvus Therapeutics, 2024). This approach offers the potential to halt disease progression specifically, avoiding the broad immunosuppression and associated side effects of traditional MS treatments (Frontiers in Immunology, 2020).

Other names

Myelin-peptide-HLA complexMyelin autoantigen-MHC complexpMHC complexMyelin-derived peptide-MHC complexMyelin-derived peptide-MHC complexes on antigen-presenting cells

Induction of antigen-specific immune tolerance through the deletion of autoreactive T cells, induction of T-cell anergy, or the expansion of regulatory T cells (Tregs) that suppress the inflammatory response against myelin.