Jennifer Loconto (4)(6)(1), Fabio Papes (4)(1), Ernie Chang (1), Lisa Stowers (5)(1), Elsy P. Jones (2), Toyoyuki Takada (7)(3), Attila Kumánovics (2), Kirsten Fischer Lindahl (2)(3) and Catherine Dulac (1)
Cell, Volume 112, Issue 5 , 7 March 2003, Pages 607-618
(1) Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
(2) Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
(3) Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
The vomeronasal organ (VNO) of the mouse has two neuronal compartments expressing distinct families of pheromone receptors, the V1Rs and the V2Rs. We report here that two families of major histocompatibility complex (MHC) class Ib molecules, the M10 and the M1 families, show restricted expression in V2R-expressing neurons. Our data suggest that neurons expressing a given V2R specifically co-express one or a few members of the M10 family. Biochemical and immunocytochemical analysis demonstrates that in VNO sensory dendrites M10s belong to large multi-molecular complexes that include pheromone receptors and 2-microglobulin (2m). In cultured cells, M10s appear to function as escort molecules in transport of V2Rs to the cell surface. Accordingly, 2m-deficient mice exhibit mislocalization of V2Rs in the VNO and a specific defect in male-male aggressive behavior. The functional characterization of M10 highlights an unexpected role for MHC molecules in pheromone detection by mammalian VNO neurons.