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The Journal of Neuroscience, October 28, 2009, 29(43):13503-13515; doi:10.1523/JNEUROSCI.0981-09.2009

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

Sebastian Thams,¹ Petter Brodin,^2 * Stefan Plantman,^1 * Robert Saxelin,¹ Klas Kärre,² and Staffan Cullheim¹

¹Department of Neuroscience and ²Strategic Research Center for Studies of Integrative Recognition in the Immune System, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden

Correspondence should be addressed to either Sebastian Thams or Staffan Cullheim, Department of Neuroscience, Retzius väg, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Email: sebastian.thams{at}ki.se or Email: staffan.cullheim{at}ki.se

Major histocompatibility complex (MHC) class I molecules have fundamental functions in the immune system. Recent studies have suggested that these molecules may also have non-immune functions in the nervous system, in particular related to synaptic function and plasticity. Because adult motoneurons express mRNAs for MHC class I molecules, we have examined their subcellular expression pattern in vivo and their role for the synaptic connectivity of these neurons. We observed immunoreactivity for classical MHC class I (Ia) protein in motoneuron somata, but the predominant expression was found in axons and presynaptically at neuromuscular junctions (NMJs). Peripheral nerve lesion induced a strong increase of motoneuron MHC class Ia (H2-K^b/D^b) mRNA, indicating a role for MHC class Ia molecules during regeneration. Accordingly, there was an accumulation of MHC class Ia proteins at the cut ends and in growth cones of motor axons after lesion. In K^b–/–D^b–/– mice (lacking MHC class Ia molecules), the time course for recovery of grip ability in reinnervated muscles was significantly delayed. Muscles from K^b–/–D^b–/– mice displayed an increased density and a disturbed distribution of NMJs and fewer terminal Schwann cells/NMJ compared with wild-type mice. A population of Schwann cells in sciatic nerves expressed the paired Ig receptor B, which binds to MHC class I molecules. These results provide the first evidence that neuronal MHC class Ia molecules are present in motor axons, that they are important for organization of NMJs and motor recovery after nerve lesion, and that their actions may be mediated via Schwann cells.

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Received Feb. 27, 2009; revised Sept. 8, 2009; accepted Sept. 11, 2009.

Correspondence should be addressed to either Sebastian Thams or Staffan Cullheim, Department of Neuroscience, Retzius väg, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Email: sebastian.thams{at}ki.se or Email: staffan.cullheim{at}ki.se

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