title: The RMA-S lymphoma mutant; consequences of a peptide loading defect on immunological recognition and graft rejection.
abstract: Experiments with mutant cell lines have underscored the role for peptide in maintenance of the structure of major histocompatibility complex (MHC) class-I molecules. The class-I molecules act as receptors for antigenic and "self" peptides derived from degraded intracellular synthesized proteins. The class-I/peptide trimeric complex is transported to the cell surface where it is scrutinized by cytotoxic T lymphocytes (CTL). The murine RMA-S mutant cell lines have a defect in class-I assembly and express markedly reduced levels of class-I molecules at the cell surface. The mutation is consistent with a defect in peptide transport from the cytosol to the place of assembly with class-I molecules. Addition of synthetic peptides to RMA-S cells and RMA-S cell lysates stimulates assembly of the class-I molecules and indicates that peptide plays a crucial role in attaining the class-I structure. Recent findings have demonstrated that class-I heavy clains (HCs) and beta 2 microglobulin (beta 2m) can assemble in absence of synthetic peptides, forming presumably "empty" (non-peptide-containing) class-I dimeric complexes, in RMA-S cells cultured at reduced temperature. The few class-I molecules present on RMA-S cultured at physiological temperature share the phenotype of "empty" class-I molecules induced at reduced temperature. This finding has allowed the re-interpretation of earlier studies and opened new ways to analyze the interaction between MHC-class-I molecules and different effector cells such as allo-specific CTLs, class-I-restricted CTLs and natural killer (NK) cells. In addition, recent data also suggest that RMA-S represents an attractive model for examining direct class-I-peptide interactions on intact cells or in cell lysates.
authors.affiliation: Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: H G
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: C
authors.initials: C
authors.lastname: Ohlén
authors.forename: P
authors.initials: P
authors.lastname: Höglund
authors.forename: L
authors.initials: L
authors.lastname: Franksson
authors.forename: K
authors.initials: K
authors.lastname: Kärre
mesh_terms: D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection; D006183:H-2 Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009368:Neoplasm Transplantation; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I