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Neurons Control Brain Immunity: Neurotrophins As Regulators Of Antigen-Presentation In Microglial Cells

Antigen presentation in the context of major histocompatibility complex (MHC) molecules is a seminal step in the initiation of specific immune responses. These proteins lack in the healthy brain rendering it a partially "immune privileged site". The reasons for this immunological peculiarity of the brain are thus far unknown. Recent work from Hartmut Wekerle's department at the Max Planck Institute of Neurobiology (in Martinsried/Germany) published in the PNAS (Neumann H., Misgeld T. et al., PNAS, 1998, 95 [10]: 5779-5784) shows that neurons might be a key player in this regulatory process by down-regulating MHC class II molecules in neighbouring microglial cells. The data suggest that neurotrophins acting via their p75 receptor are involved in this process, demonstrating an immunological function for these signalling molecules.

MHC class II antigens are dimeric glycoproteins, which are loaded with pathogen derived antigenic peptides within so called antigen-presenting cells (APCs). The exposure of MHC-antigen complexes on the surface of APCs and their recognition by T cell antigen receptors is one of the initiating events of a specific immune response. Astonishingly these important immune molecules that can be found constitutively in most tissues of the body lack in the normal central nervous system. Only under pathological conditions they are induced, most prominently in microglial cells that represent the major APC of the brain. Not only inflammatory lesions to the brain can initiate this state of increased "immune responsiveness" but also neurodegenerative conditions of many kinds.

Using explant cultures of neuronal tissue and a confocal laser scanning microscopy based image
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Contact: Harald Neumann
hneumann@neuro.mpg.de
+49-89-8578-3561
Max-Planck-Gesellschaft
8-Jun-1998


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