Characterization of monoclonal antibodies against the human immunodeficiency virus matrix protein p17gag: identification of epitopes exposed at the surfaces of infected cells.

摘要

Eight monoclonal antibodies reactive with the matrix protein of human immunodeficiency virus type 1 (HIV-1), p17gag, were isolated from rats which had been immunized with solubilized HIV-1 lysate. The epitope specificities of these antibodies were determined with a series of synthetic peptides representing overlapping regions of p17. Six of the antibodies were mapped to three distinct regions of p17, while two antibodies (G11g1 and G11h3) reacted only with intact recombinant p17, suggesting that they were directed against conformational or discontinuous epitopes. All the antibodies bound to HIV-infected cells which had been permeabilized with acetone, but only G11g1 and G11h3 reacted with live HIV-infected cells. Specificity studies with diverse virus strains demonstrated that these two antibodies recognized distinct epitopes, one which was group specific for HIV-1, and one which was shared with HIV type 2 and simian immunodeficiency virus. Binding competition studies indicated that these epitopes were proximal in native p17. Despite their reactivity with intact cells, these two antibodies did not possess appreciable virus-neutralizing activity. These results indicate that a form of p17 is expressed on the surfaces of live HIV-infected cells which is accessible to some, but not all, antibodies against p17. These cell surface molecules may play a role in the generation of antibodies against p17gag that are characteristic of early stages of HIV infection, and they may act as natural targets for the immune system and as potential targets for immunotherapy of HIV-infected cells.