Distinct Pathways for Constitutive Endocytosis of Fully Conformed and Non‐conformed L d Molecules[Note 1. Presented at the VIII International Congress of Reproductive Immunology, ...]

PROBLEM: To characterize the constitutive internalization of major histocompatibility complex (MHC) class I molecules, we have studied the expression of completely conformed (full) and unconformed (empty) L d molecules on non‐polarized murine P815 cells. METHODS OF STUDY: Spontaneous endocytosis of L d molecules was induced by cycloheximide, an inhibitor of protein synthesis, and their disappearance from the cell surface was determined by flow cytometry. In order to investigate the mechanism of internalization, a palette of inhibitors of endocytosis and vesicular transport was used. RESULTS: Inhibitors of clathrine endocytosis did not influence the internalization of L d molecules. Inhibitors of caveolar endocytosis and inhibitors of endolysosomal degradation prevented down‐regulation of empty, but not of full L d molecules. CONCLUSIONS: Empty L d molecules are internalized mostly by caveolar endocytosis and full L d molecules use a different pathway, neither clathrine‐mediated nor caveolar. After internalization, full L d molecules are probably degraded and empty L d molecules recycle between endosomal compartment and the cell surface before they enter into the degradation compartment.