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 molecules, 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 degrees C) promotes assembly, and results in a high level of cell surface expression of H-2/beta 2-microglobulin complexes that do not present endogenous antigens, and are labile at 37 degrees C. They can be stabilized at 37 degrees 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.
Ljunggren
H G
HG
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Stam
N J
NJ
Ohlén
C
C
Neefjes
J J
JJ
Höglund
P
P
Heemels
M T
MT
Bastin
J
J
Schumacher
T N
TN
Townsend
A
A
Kärre
K
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001692:Biological Transport; D002462:Cell Membrane / Q000276:immunology; D003080:Cold Temperature; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D008223:Lymphoma; D046911:Macromolecular Substances; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000378:metabolism
D006183:H-2 Antigens; D046911:Macromolecular Substances; D001613:beta 2-Microglobulin