The RMA-S lymphoma mutant; consequences of a peptide loading defect on immunological recognition and graft rejection.
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.
Ljunggren
H G
HG
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Ohlén
C
C
Höglund
P
P
Franksson
L
L
Kärre
K
K
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
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I