Selective turnover and shedding of H-2K and H-2D antigens is controlled by the major histocompatibility complex....

Lactoperoxidase-catalyzed cell surface radioiodination and incorporation of [3H]-leucine were employed to radiolabel H-2K and H-2D antigens of murine spleen cells. The fate of H-2 antigens was monitored by in vitro culture of labeled cells and isolation of labeled antigens from detergent lysates of the cells and culture supernates obtained at different times during culture. H-2Kk antigens were found to be rapidly turned over and shed by CBA/J cells, whereas the turnover of H-2Dk antigens was extremely slow. Analysis of the membrane residence times of surface-labeled H-2K and H-2D antigens on spleen cells from various H-2-congenic and -recombinant strains demonstrated variations in the shedding rates of H-2K and H-2D antigens, which were controlled by genes mapping in the major histocompatibility complex. These variations show a striking correlation with published, genetically controlled quantitative variations in the cytotoxic response of T lymphocytes to chemically modified or virus-infected syngeneic cells.