The fate of the three subunits of major histocompatibility complex class I molecules.
At the surface of the murine T lymphoma cell line RMA-S, the expression of "empty" class I molecules can be dramatically enhanced by culture at 26 degrees C. These class I molecules are unstable following transfer to 37 degrees C unless they are loaded with exogenously added peptides. Class I heterodimers that have failed to bind peptide ("empty" class I molecules) dissociate and the class I heavy chains are degraded. Internalization, if it precedes breakdown, would be the rate-limiting step. Radioiodinated peptides (VSV NP 8-mer or Sendai NP 9-mer) dissociate from the class I molecules in the absence of exogenous peptide or beta 2 microglobulin and appear in the medium. Release of the iodinated peptides does not result in a reduction in the quantity of stable assembled class I molecules. This paradox may be explained by a more rapid off-rate for radioiodinated peptides, when compared with their unlabeled counterparts, which constitute about 99% of the total in our radiolabeled preparations. In the medium the peptide is rapidly modified by serum- and cell-derived proteases. The short half-life of empty class I molecules and of free ligand would effectively preclude sensitization of innocent bystanders for lysis by cytotoxic T lymphocytes.
Neefjes
J J
JJ
The Netherlands Cancer Institute, Amsterdam.
Smit
L
L
Gehrmann
M
M
Ploegh
H L
HL
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D006207:Half-Life; D006358:Hot Temperature / Q000009:adverse effects; D051379:Mice; D008969:Molecular Sequence Data; D010222:Parainfluenza Virus 1, Human; D011233:Precipitin Tests; D013601:T-Lymphocytes / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology; D001613:beta 2-Microglobulin / Q000276:immunology / Q000378:metabolism
D001798:Blood Proteins; D006183:H-2 Antigens; D014764:Viral Proteins; D001613:beta 2-Microglobulin