Function of macrophages in genetic control of immune responsiveness

Macrophages serve an essential but poorly understood role in the cellular and molecular events that underlie immune competence. Antigenic proteins are now known to bind initially to macrophages prior to their recognition by T lymphocytes. Antigen uptake by macrophages is a metabolism-dependent event that results in an association of the antigen or a fragment thereof with a product of genes linked to the major histocompatibility complex of the species. For recognition of this associative form of antigen and self to result in cell proliferation, a direct physical interaction of antigen-bearing macrophage and lumphocyte must occur. Soluble forms of the altered antigen complexed to self may, however, function in nonproliferative T cell activation phenomenon. Using antigens of defined structure, it is possible to derive data which indicate that genetic control of immune responsiveness resides at the level of the antigen-presenting cell, thus indicating that these latter cells have profound discriminatory influences on host immune competence.