Empty MHC class I molecules come out in the cold

• Published in: Nature (London) 1990-08, Vol.346 (6283), p.476-480
• Main Authors: Ljunggren, Hans-Gustaf, Stam, Nico J, Öhlén, Claes, Neefjes, Jacques J, Höglund, Petter, Heemels, Marie-Thérèse, Bastin, Judy, Schumacher, Ton N. M, Townsend, Alain, Kärre, Klas, Ploegh, Hidde L
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigens; Assembly; beta 2-Microglobulin - metabolism; Biodegradation; Biological and medical sciences; Biological Transport; Body temperature; Cancer; Cell culture; Cell Membrane - immunology; Cell surface; Cold Temperature; Cytotoxicity; Fundamental and applied biological sciences. Psychology; Fundamental immunology; H-2 Antigens - immunology; H-2 Antigens - metabolism; Histocompatibility antigen H-2; Histocompatibility antigens (hla, h-2 and other systems); Humanities and Social Sciences; letter; Lymphoma; Macromolecular Substances; Major histocompatibility complex; Mice; Molecular immunology; multidisciplinary; Mutation; Peptides; Protein Binding; Protein Conformation; Protein Processing, Post-Translational; Science; Science (multidisciplinary); T-Lymphocytes, Cytotoxic - immunology; Temperature effects; Tumor Cells, Cultured
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/346476a0

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 molecules 1 , 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–2K b or D b . 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.