MONOCLONAL C-MYC TRANSFORMED MACROPHAGE CELL-LINES .1. HETEROGENEITY IN ABILITY TO PROCESS AND PRESENT ANTIGEN

Processing of proteins into immunogenic forms and their subsequent pre sentation to T cells are mediated by APC. Monocytes and macrophages ha ve long been recognized as one of the APC types. However, little is kn own about whether functional heterogeneity in processing and presentat ion exist within the monocyte/macrophage population. Past difficulties in obtaining clonal representatives of these populations have limited investigations in this regard. The c-myc-containing retrovirus MRV, p reviously shown to immortalize murine macrophages, was used to generat e a large panel of macrophage cell clones. Differences observed in cel l surface antigen expression and morphology demonstrated phenotypic he terogeneity among these clones. Functional heterogeneity was also obse rved both before and after IFN-gamma and IL-4 stimulation. The clones differ in their capacity to present several nominal antigens to T cell hybridomas. When parallel variation in ability to present both a nomi nal antigen and a peptide representing the epitope for which a T cell hybridoma was specific was observed among the clones, this variation c orrelated with the levels of surface MHC class II antigen the clones e xpressed. In contrast, diversity in the ability to process and present certain nominal antigens among clones that all presented the correspo nding antigenic peptide with similar efficiency did not appear to be d ue to differences in levels of surface MHC class II molecules. Our res ults suggest that the macrophage clones are heterogeneous in their abi lity to both process and present several antigens. The ability to obta in macrophage tissue culture cell lines displaying phenotypic and func tional heterogeneity should allow insight into the impact of normal ma crophage heterogeneity on the outcome of immune responses in vivo.