The Impact of Antigen Presentation on BBB Disruption and Neuroinflammation

Blood-brain barrier (BBB) disruption is a potentially deadly complication of numerous neurological diseases as diverse as cerebral malaria, dengue hemorrhagic fever, tauopathies, multiple sclerosis, schizophrenia, Parkinson's disease, narcolepsy, and COVID-19. Neuroinflammation and immune cell infiltration are both drivers and consequences of BBB disruption. In this review, we will provide an overview of how brain-infiltrating T-cell responses engage the cellular components of the neurovascular unit (NVU), which regulates the BBB in preclinical models. This will provide context on how the immune system can contribute to vascular leakage and neuropathology in neurological diseases. We will discuss how discrete major histocompatibility complex (MHC) class I and class II molecules on NVU cell types govern T-cell entry, retention, and barrier disruption in neuroinflammatory diseases. Finally, we will summarize our current understanding of how discrete human leukocyte antigen (HLA) genes associate with specific neurological diseases characterized by neuroinflammation and BBB disruption.