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

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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°C. These class I molecules are unstable following transfer to 37°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 heavychains are degraded. Internalization, if it precedes breakdown, would be the rate‐limiting step.Radioiodinated peptides (VSV NP8‐mer or Sendai NP9‐mer) dissociate from the class I molecules in the absence of exogenous peptide or β2 microglobulin and appear in the medium. Release of the iodinated peptides does notresult 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 offree ligand would effectively preclude sensitization of innocent bystanders for lysis by cytotoxic T lymphocytes.