title: Peptide ligand-induced conformation and surface expression of the Ld class I MHC molecule.
abstract: Newly synthesized major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum are thought to bind peptides of foreign and endogenous antigens. Several lines of evidence indicate that beta-2 microglobulin (beta 2m) and/or peptide ligand participate in the intracellular transport and surface expression of class I molecules, but the nature of their involvement is still unclear. Here we present evidence that culturing non-mutant cells (fibroblast, thymoma or mastocytoma) with a peptide ligand specific for the Ld class I molecule of the mouse leads to a dramatic (fourfold) and specific induction of Ld surface expression. Surprisingly, this peptide ligand-induced expression of Ld does not result in an increased intracellular association of Ld with beta 2m. These findings demonstrate that the previously reported decrease in surface expression of Ld results from its failure to be saturated with endogenous self-peptide ligands. This unique feature of Ld could also contribute to the fact that several virus-specific cytotoxic T cell responses have been found to be Ld-restricted.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: W R
authors.initials: WR
authors.lastname: Lie
authors.forename: N B
authors.initials: NB
authors.lastname: Myers
authors.forename: J
authors.initials: J
authors.lastname: Gorka
authors.forename: R J
authors.initials: RJ
authors.lastname: Rubocki
authors.forename: J M
authors.initials: JM
authors.lastname: Connolly
authors.forename: T H
authors.initials: TH
authors.lastname: Hansen
mesh_terms: D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000276:immunology*; D003587:Cytomegalovirus; D005347:Fibroblasts / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007739:L Cells; D012515:Mast-Cell Sarcoma; D051379:Mice; D008968:Molecular Conformation; D009363:Neoplasm Proteins / Q000276:immunology / Q000494:pharmacology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D013945:Thymoma; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000276:immunology / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000502:physiology
chemical_list: D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D009363:Neoplasm Proteins; D010455:Peptides; D014764:Viral Proteins; D001613:beta 2-Microglobulin