GENOMIC ORGANIZATION OF THE MOUSE LMP-2 GENE AND CHARACTERISTIC STRUCTURE OF ITS PROMOTER

Major histocompatibility complex (MHC) class-I molecules present antig enic peptide fragments to cytotoxic T-cells. The peptides are generate d in the course of antigen processing from endogenously synthesized cy tosolic proteins, and transported into the endoplasmic reticulum to as sociate with an MHC class-I molecule. So far, at least four genes, Lmp -2,7, and Tap-1, -2, have been identified between the Pb and Ob genes of the mouse MHC class-II region. The genomic organizaion of mouse Lmp -2, a gene encoding a subunit of a large intracellular protein complex , was studied. A genomic clone has been isolated that covers the entir e mouse Lmp-2 gene. We have determined the nucleotide sequence of the region encompassing the whole Lmp-2 gene and three exons of Tap-1, whi ch spans 8 kb in the mouse genome. The two genes are situated in oppos ite directions. The transcription start points (tsp) of the two genes, identified by primer extention analysis, are only 118 bp apart. Both promoter regions upstream from the tsp have neither TATA consensus seq uences nor other regulatory elements, like an interferon-response elem ent, in spite of their interferon-inducible expression. The Lmp-2 sequ ence from a non-obese diabetic (NOD) mouse, a model animal for autoimm une diabetes, was compared with that from a Balb/c mouse.