Functional diversity of Ia epitopes on macrophages

A panel of monoclonal antibodies directed against various epitopes of mouse Iak was used to block functions mediated by Iak on CBA/J macrophages in two different assay systems. The first system was the recently described proliferation inhibition of an H-2k T cell clone (8.1.11.2) by a combination of CBA/J (nonactivated) macrophages and anti-Iak (Kedar, I. et al. J. Immunol. 1986. 136: 3166). The second system was the well known macrophage cytotoxicity induced by interferon against various transformed cells. We found that anti-Iak antibodies directed against serological specificity number 2 (on the alpha chain of IA) blocked the proliferative stimulus of the macrophage Iak for the 8.1.11.2 T cell clone. Both an IgG and an IgM antibody with this specificity were effective, whereas seven other anti-Iak (including several for other specificities on the alpha chain of IA) were not. Conversely, two different monoclonal anti-Iak antibodies directed against serological specificity number 17 (on the beta chain of IA) inhibited the cytolytic activity of the activated macrophages for the 8.1.11.2 T cell clone as well as the P815 (H-2d) mastocytoma as target, whereas four other antibodies were ineffective in this regard. In addition to providing evidence that Ia may participate in the cytolytic activity of activated macrophages, these studies demonstrate that different epitopes of Iak on macrophages are differentially involved in different biological functions.