CRYSTAL STRUCTURE OF MURINE CD1d1. Ian A. Wilson1, Zonghao Zeng1, A. Raul Castaño1, Brent Segelke1, Enrico A. Stura1, Per A. Peterson2, 1The Scripps Research Institute, Dept. of Molecular Biology, 10666 No. Torrey Pines Rd., La Jolla, CA 92037, 2R. W. Johnson Pharmaceutical Research Institute, 3535 General Atomics Court, Suite 100, San Diego, CA 92121.
Murine CD1d1 is a member of a family of cell surface glycoproteins that are distantly related to MHC molecules.1 CD1 molecules are encoded outside the MHC and have restricted tissue expression.1,2 The precise function of CD1 molecules is as yet unknown but CD1 is believed to represent a novel class of antigen presenting molecules of the immune system. Like MHC class I presenting cells, CD1 presenting cells can illicit a cytolytic T-cell medicated immune response.3,4 Two T-cell lines reactive to murine CD1d have been phenotyped; the first has a conventional MHC class I reactive phenotype [[alpha]]/[[beta]] CD4-/CD8+ TCR+ and the second has phenotype [[alpha]]/[[beta]] CD4-/CD8- TCR+.5,6
The crystal structure of a type II murine CD1 molecule, CD1d1, has been determined to 2.8Å by molecular replacement and refined to a crystallographic R-value of 19%. Each of the four domains of the structure are structurally homologous with the corresponding domains of the known MHC and MHC-like molecules. With the exception of the small H1 helix of class I MHC antigens all of the secondary structural elements of the class I MHC are preserved, There are, however, substantial differences in the shape and chemical properties of the putative ligand binding groove suggesting a different mode of ligand binding.
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