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

Ofer Zohar^1,*, Yoram Reiter, Jack R. Bennink, Avital Lev, Sebastiano Cavallaro, Sabrina Paratore, Chaim G. Pick^¶, Gary Brooker^|| and Jonathan W. Yewdell

^* Blanchette Rockefeller Neurosciences Institute, Johns Hopkins University Montgomery County Campus, Rockville, MD 20850; Faculty of Biology, Technion, Israel Institute of Technology, Haifa, Israel; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892; Functional Genomics Center, Institute of Neurological Sciences, Italian National Research Council, Catania, Italy; ^¶ Department of Anatomy and Anthropology, Tel-Aviv University Sackler School of Medicine, Tel-Aviv, Israel; and ^|| Department of Chemistry, Johns Hopkins University Microscopy Center, Montgomery County Campus, Rockville, MD 20850

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Ofer Zohar, Blanchette Rockefeller Neurosciences Institute, Johns Hopkins University Montgomery County Campus, 9601 Medical Center Drive, Rockville, MD 20850. E-mail address: zohar{at}brni-jhu.org

² Abbreviations used in this paper: MHC-I, MHC class I; B6, C57BL/6J.