Major histocompatibility complex class I proteins in brain development and plasticity

Proper development of the central nervous system (CNS) requires the establishment of appropriate connections between neurons. Recent work suggests that this process is controlled by a balance between synaptogenic molecules and proteins that negatively regulate synapse formation and plasticity. Surprisingly, many of these newly identified synapse-limiting molecules are classic 'immune' proteins. In particular, major histocompatibility complex class I (MHCI) molecules regulate neurite outgrowth, the establishment and function of cortical connections, activity-dependent refinement in the visual system, and long-term and homeostatic plasticity. This review summarizes our current understanding of MHCI expression and function in the CNS, as well as the potential mechanisms used by MHCI to regulate brain development and plasticity.