T cells do not see antigen directly, but rather recognize antigen only when displayed by an antigen-presenting cell (APC). APC take up, internalize, and degrade antigen and present the relevant antigenic fragment in association with class II major histocompatibility complex (MHC) molecules to antigen-specific T cells. In addition to presenting the antigenic fragment-MHC complex to T cells, APC must also provide a variety of antigen-nonspecific influences to T cells for antigen recognition to result in T-cell activation. These influences include the effects of various cytokines and signals transmitted by a number of nonspecific receptor-ligand interactions. Traditionally, cells of bone marrow origin that express class II MHC molecules, such as mononuclear phagocytes and B lymphocytes, have been regarded as the only APC. Recently, however, it has been suggested that under various physiologic and pathologic conditions, other tissue cells may develop the capacity to express class II MHC molecules and function as APC. The capacity of these cells to function as APC, however, varies widely, depending on the cell type examined. One determinant of the capacity of a cell to function as an APC appears to be its ability to provide antigen-nonspecific signals. Cells with limited abilities to provide these signals have limited APC function. Indeed, it has been suggested that such cells may induce antigen-specific tolerance. In contrast, cells with the capacity to deliver these signals function as fully competent APC. The functional phenotype of the responding T cell may also vary, depending on the nonspecific signals provided by the APC. Some APC may preferentially stimulate antigen-specific T cells that promote the immune response, whereas others promote the activation of suppressor T cells, thereby limiting the response. Thus, it is likely that cells that are not of bone marrow origin play a role in normal immune responses. Moreover, they may also be important in the development of certain forms of autoimmunity.