The fate of the three subunits of major histocompatibility complex class I molecules.

Abstract

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.