Myelin-derived peptide–Major Histocompatibility Complex class II complex (Myelin-pMHC II)

The Myelin-derived peptide–Major Histocompatibility Complex (MHC) class II complex is a specialized molecular assembly presented on the surface of antigen-presenting cells (APCs), such as dendritic cells and B cells. These complexes consist of specific epitopes derived from myelin proteins—primarily myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG)—bound to MHC class II molecules (e.g., HLA-DRB1*15:01 in humans). In the context of autoimmune diseases like Multiple Sclerosis (MS), these complexes are inappropriately recognized by autoreactive CD4+ T cells, triggering an inflammatory cascade that leads to the destruction of the myelin sheath in the central nervous system (PubMed: 31209224). Consequently, this complex serves as a primary target for antigen-specific immunotherapies (ASIT) designed to restore immune homeostasis. Therapeutic approaches include the use of soluble pMHC monomers, pMHC-coated nanoparticles (Navacims), or tolerogenic APCs that present these complexes in a non-costimulatory environment to induce T-cell anergy or promote the differentiation of regulatory T cells (Tregs) (Nature Communications: 10.1038/s41467-019-10517-y). Unlike broad immunosuppressants, targeting the myelin-pMHC II complex aims to selectively silence the pathogenic immune response while leaving the rest of the immune system intact. This precision approach is intended to reduce the risk of opportunistic infections and other side effects associated with systemic immune suppression (Frontiers in Immunology: 10.3389/fimmu.2020.01141).

Other names

Myelin peptide-HLA-DR complexMyelin-pMHCAutoreactive pMHC complexMyelin-HLA complex

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