HLA polymorphism in neuroimmune diseases: linking antigen presentation to neuroinflammatory programs
TL;DR
This evidence-bounded synthesis identifies where HLA mechanisms are established, suggestive, or still inferred from association across multiple sclerosis, neuromyelitis optica spectrum disorder, Guillain–Barré syndrome, narcolepsy, autoimmune encephalitis, and myasthenia gravis.
Abstract
Human leukocyte antigen (HLA) polymorphism shapes antigen presentation and susceptibility to immune-mediated disease. In neuroimmune disorders, a central question is how HLA-dependent antigen visibility becomes disease-specific immunity and tissue injury. In this Review, we integrate genetic, molecular, cellular, and clinical evidence across multiple sclerosis (MS), neuromyelitis optica spectrum disorder, Guillain–Barré syndrome, narcolepsy, autoimmune encephalitis, and myasthenia gravis. The HLA-DR15-MS axis is the most mechanistically resolved example, linking allele-specific peptide display to autoreactive T-cell repertoires and convergent Epstein–Barr virus-related immune pathways. In other disorders, this upstream principle operates through distinct effectors, target tissues, molecular subtypes, and ancestral contexts, while causal peptide-receptor complexes often remain unresolved. We therefore separate association strength from mechanistic resolution and position glial activation and tissue injury mainly as downstream, context-dependent processes. This evidence-bounded synthesis identifies where HLA mechanisms are established, suggestive, or still inferred from association.