ANTIGENIC MODULATION IN VITRO I. Fate of Thymus-Leukemia (TL) Antigen-Antibody Complexes Following Modulation of TL Antigenicity from the Surfaces of Mouse Leukemia Cells and Thymocytes*

Cell surface antigens of the thymus-leukemia (TL) 1 system in the mouse are detectable only on thymocytes and cells of certain leukemias {1-3). Although TL antigens are not expressed on thymocytes of all mouse strains, leukemias developing in T L strains may be phenotypically TL+, suggesting that TL structural genes may be present in all mouse strains, and possibly in all cells (2). The appearance of TL antigens on thymocytes and leukemia cells presumably results from activation or de-repression of these structural genes by regulatory genes (4). Initial at tempts to immunize T L mice against their own TL+ leukemias by making them hyperimmune to TL antigens were unsuccessful, and when leukemia cells were recovered from these mice they had become phenotypically T L (1). The cells remained T L as long as they were passaged continually in hyperimmune mice, but regained the TL+ phenotype when returned to nonimmunized mice. This reversible loss of TL antigenicity has been termed antigenic modulation, and occurs rapidly when cells are exposed to TL antiserum either in vivo (1, 5) or in vitro at 37°C (6), cell surface an'tigenicity being measured by the cytotoxic activity of a subsequent exposure of cells to fresh TL antiserum in the presence of lytic complement (C'). Analysis of antigenic modulation in vitro suggested to Old et al. (6) that modulated TL antigen-antibody complexes were lost from the cell surface by a process requiring cellular metabolic activity. Loss of these complexes could presumably occur either by exfoliation from the cell surface or internalization by pinocytosis. Yu and Cohen (7) have suggested that pinocytosis may account for the apparent loss of modulated TL antigens. Although antigenic modulation has not been demonstrated in the same