The RMA-S lymphoma mutant; consequences of a peptide loading defect on immunological recognition and graft rejection

Int J Cancer Suppl. 1991;6:38-44. doi: 10.1002/ijc.2910470711.

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.

MeSH terms

  • Animals
  • Cell Line
  • Cytotoxicity, Immunologic
  • Graft Rejection*
  • H-2 Antigens / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Killer Cells, Natural / immunology
  • Lymphoma / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Neoplasm Transplantation
  • Phenotype
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • H-2 Antigens
  • Histocompatibility Antigens Class I