PRESENTATION OF EXOGENOUS ANTIGENS BY MACROPHAGES - ANALYSIS OF MAJORHISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II PRESENTATION AND REGULATION BY CYTOKINES

There is an antigen presenting cell (APC) in the lymphoid organs capab le of presenting exogenous antigen (Ag) with major histocompatibility complex (MHC) class I molecules. This study was initiated to isolate c lones of these APC to definitively establish their phenotype and to fu rther study their properties. Murine bone marrow macrophages (BM M Phi ) were immortalized by overexpressing myc and raf oncogenes. Five BM M Phi cell lines were generated that are phagocytic and expressed at th eir surface M Phi differentiation Ag. All five cell lines processed an d presented exogenous ovalbumin (OVA) with MHC class I molecules. They all presented OVA-linked to a phagocytic substrate 10(2)-10(4)-fold m ore efficiently than soluble Ag. Clonal isolates of two of the M Phi c ell lines had an identical phenotype and functional properties as the uncloned lines. These results definitively establish that M Phi are AP C with the capacity of presenting exogenous Ag with MHC class I molecu les. Interferon (IFN)-gamma interleukin-4, granulocyte-macrophage colo ny stimulating factor and lipopolysaccharide either alone or in combin ation induced little or no augmentation and in some cases decreased pr esentation of exogenous OVA with MHC class I. In contrast, all of M Ph i activating factors increased MHC class I expression. Moreover, IFN-g amma increased the presentation of cytosolic OVA, demonstrating differ ences between the presentation of cytosolic Ag versus exogenous Ag wit h MHC class I. Finally, some lines constitutively processed and presen ted exogenous OVA with MHC class II while others only presented after stimulation with IFN-gamma. These results demonstrate that the pathway s involved in the presentation of exogenous Ag with MHC class I and cl ass II are independently regulated and that a cloned cell is capable o f presenting exogenous Ag through both pathways.