Antigen presentation at the blood–brain barrier amplifies neuroinflammation

Immune surveillance of the central nervous system (CNS) is regulated by the brain barriers. Antigen presentation at the blood-brain barrier (BBB) has been proposed to promote antigen-specific T-cell entry into the CNS, largely based on in vitro studies. Recent in vivo and transcriptomic studies call for a reassessment of this concept. In healthy mouse and human CNS endothelium, major histocompatibility complex (MHC) class I expression is low, and MHC class II is minimal to absent. During neuroinflammation, brain microvascular endothelial cells (BMECs) can acquire antigen-presenting features, predominantly in the context of strong or prolonged inflammation. We propose that BMEC antigen presentation amplifies vascular pathology rather than initiating CNS T-cell entry during immune surveillance or disease.