Physical and pharmacologic inhibition of the shedding of I-A antigens.

Lactoperoxidase-catalyzed cell surface radioiodination was employed to radiolabel murine splenic lymphocyte membrane Ia antigens (I-Ak, I-Ek) and IgM. The catabolism of labeled membrane proteins was monitored by in vitro culture of the labeled cells, detergent lysis at intervals during culture, and immunoprecipitation of labeled antigens. Treatment of cells with UV irradiation, heat treatment, glutaraldehyde fixation, and colchicine reduces the shedding and/or expression of cell surface antigens and in particular those of the I-A subregion. Considered in physiological terms, we suggest that in addition to the amount of I-A antigen present on antigen-presenting cells, turnover and shedding of I-A antigens may be important for the stimulation of an immune response by allogeneic cells and in allowing a cell with receptors for foreign antigen (x) as well as for self I-A to find antigen x on I-A antigen-bearing cells.