Cutting Edge: MHC Class I–Ly49 Interaction Regulates Neuronal Function

Abstract

MHC class I molecules (MHC-I) have been implicated in nervous system development in the mouse. In this study we present evidence for the interaction of MHC-I with the NK cell receptor Ly49 in primary cortical neuronal cultures. We show that MHC-I and Ly49 are expressed on neuronal soma and axon surfaces, with Ly49 also present on dendrites. Anti-MHC-I Abs reduce synapsin-I expression and enhance neurite outgrowth and neuronal death. Conversely, anti-Ly49 mAbs increase synapsin-I expression, reduce neurite outgrowth, and promote neuron viability. Because we show that Ly49 genes are selectively expressed in the adult brain, these findings suggest an unsuspected role for the MHC-I-Ly49 interaction in the development and function of the brain.

Classical Major Histocompatibility Complex Class I Molecules in Motoneurons: New Actors at the Neuromuscular Junction

“…The most well known receptor for MHC class I is the CD3 associated T-cell receptor (TCR), and recent publications indicate that PIRs and members of the Ly49 receptor family act as receptors for neuronally expressed MHC class I molecules (Syken et al, 2006;Zohar et al, 2008). We thus found it important to search for expression of such receptors in the nerve and muscle.…”

“…There is accumulating evidence that immune molecules are used by neurons and glia in the CNS to modulate synaptic function and plasticity, in particular during development (Huh et al, 2000;Oliveira et al, 2004;Syken et al, 2006;Stevens et al, 2007;Zohar et al, 2008). Because synaptic dysfunction is a fundamental feature of neurodevelopmental and neurodegenerative diseases, it is important to understand how immune molecules in CNS cells exert their effects on synapses.…”

H2-K b and H2-D b regulate cerebellar long-term depression and limit motor learning

“…Whereas functional T cell receptors are not thought to be expressed by neurons (44), neuronal expression of other MHCI receptors including PirB (45), Ly49 (46), and Kir (47) has now been seen. However, in mice with deficiencies affecting known MHCI receptors expressed in neurons (e.g., CD3 Ϫ/Ϫ and PirB ⌬/⌬ ; Fig.…”

MHC Class I Limits Hippocampal Synapse Density by Inhibiting Neuronal Insulin Receptor Signaling

“…Several immunoreceptors for MHCI have been detected in the brain (Syken and Shatz, 2003;Bryceson et al, 2005;Syken et al, 2006;Zohar et al, 2008), and at least one, paired Ig-like receptor B (PirB), can bind to neuronal MHCI. However, mice expressing a dominant-negative form of PirB, unlike MHCI-deficient mice, have normal retinogeniculate synapse elimination (Syken et al, 2006), indicating that MHCI uses other signaling pathways to regulate connectivity in the developing nervous system.…”