Molecular Basis for the Immune Regulatory Receptor System

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Paired immunoglobulin-like receptor (PIR)-B, an immunoreceptor tyrosine-based inhibitory motif-harboring receptor for MHC class I molecules, could participate in the regulation of B-1 cells, because PIR-B expression is several times higher in B-1 cells than in B-2 cells or conventional B cells. Recent unexpected findings pointed to a novel inhibitory role of PIR-B in neurite regeneration through binding to three axonal outgrowth inhibitors of myelin including Nogo. Thus, it becomes interesting to determine whether the actions of the inhibitory myelin proteins and MHCI could coexist or be mutually exclusive as to the PIR-B-mediated immune and neural cell inhibition. We studied this subject and obtained data supporting the coexistence of Nogo- and MHCI-mediated inhibition. We now propose a novel mechanism by which PIR-B-mediated regulation is achieved dually via MHCI and Nogo in cells of the immune system.