EMPTY MHC CLASS-I MOLECULES COME OUT IN THE COLD

MAJOR histocompatibility complex (MHC) class I molecules present antigen by transporting peptides from intracellularly degraded proteins to the cell surface for scrutiny by cytotoxic T cells. Recent work suggests that peptide binding may be required for efficient assembly and intracellular transport of MHC class I molecules1, but it is not clear whether class I molecules can ever assemble in the absence of peptide. We report here that culture of the murine lymphoma mutant cell line RMA-S at reduced temperature (19-33 °C) promotes assembly, and results in a high level of cell surface expression of H-2/β2-microglobulin complexes that do not present endogenous antigens, and are labile at 37 °C. They can be stabilized at 37 °C by exposure to specific peptides known to interact with H-2Kb or Db. Our findings suggest that, in the absence of peptides, class I molecules can assemble but are unstable at body temperature. The induction of such molecules at reduced temperature opens new ways to analyse the nature of MHC class I peptide interactions at the cell surface. © 1990 Nature Publishing Group.