Myelin-derived antigenic peptides presented by HLA-DRB1*15:01 (Myelin-HLA-DRB1*15:01)

The complex formed by myelin-derived antigenic peptides presented by HLA-DRB1*15:01 is a pivotal immunological target in the study and treatment of Multiple Sclerosis (MS) (International Multiple Sclerosis Genetics Consortium, 2011). HLA-DRB1*15:01 is the most significant genetic risk factor for MS, and its primary role is the presentation of self-antigens, specifically fragments of myelin proteins like Myelin Basic Protein (MBP) and Myelin Oligodendrocyte Glycoprotein (MOG), to the immune system (Wucherpfennig et al., 1994; Nature Reviews Neurology, 2018). This presentation leads to the activation of autoreactive CD4+ T cells, which infiltrate the central nervous system and orchestrate the destruction of the myelin sheath (Frontiers in Immunology, 2020). Because this interaction is highly specific to the disease process, it serves as a focal point for antigen-specific immunotherapies (ASIT). These therapies, such as soluble peptide mixtures (e.g., ATX-MS-1467) or nanoparticle-delivered antigens (e.g., ANK-700), aim to reprogram the immune system to recognize these complexes as "self" again, thereby inducing tolerance (Journal of Neuroinflammation, 2021). Unlike traditional disease-modifying therapies that broadly suppress the immune system, targeting the myelin-HLA-DRB1*15:01 complex offers the potential for a more precise intervention with a reduced risk of opportunistic infections.

Other names

HLA-DR15-myelin peptide complexMBP/HLA-DRB1*15:01 complexMOG/HLA-DRB1*15:01 complexPLP/HLA-DRB1*15:01 complexMyelin-HLA-DR2 complexpMHC-II complex

Induction of antigen-specific immune tolerance through the promotion of regulatory T cells (Tregs), induction of T-cell anergy, or competitive displacement of encephalitogenic peptides from the HLA binding groove (Nature Reviews Neurology, 2018; Journal of Neuroinflammation, 2021).