Possible Function of Neuronal Leucine-Rich Repeat Protein 3（ NLRR3） in Primary Immune Response

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Contact between dendritic cells（ DCs） and resting T cells is essential for initiation of the primary immuneresponse. In this study, we examined whether neuronal leucine-rich repeat protein 3 （NLRR3）, a receptor involvedin nerve system development, participates in DC-T cell binding and T-cell activation. We confirmed that NLRR3is expressed on naive T cells. NLRR3 contains an Arg-Gly-Asp （RGD） motif in its amino acid sequence, for whichseveral integrins can be considered as potential ligands. Indeed, monocyte-derived DCs expressed several integrinsthat can bind to the RGD motif. Functionally, DC-induced resting allogeneic T-cell proliferation was partially inhibitedby addition of integrin-specific antibodies and synthetic RGD peptides, indicating that RGD-containing molecules,including NLRR3 and several integrins, at least participate in the events of the initial primary immune responseinvolving naive T cells and DCs. Furthermore, DCs were shown to bind directly to NLRR3-transfected Chinesehamster ovary cells in a NLRR3-dependent manner, and the binding was removed in the presence of integrin-specifi cantibodies. These data suggest that NLRR3 plays an important role in initiation of the primary immune response.