MAPPING OF IMMUNODOMINANT EPITOPES OF THE HIV-1 AND HIV-2 INTEGRASE PROTEINS BY RECOMBINANT PROTEINS AND SYNTHETIC PEPTIDES

Different parts of the human immunodeficiency virus type 1 and type 2 (HIV-1 and HIV-2) integrase proteins were expressed as TrpE fusion proteins in Escherichia coli and used to screen human sera. In the immunoblot, all HIV/integrase-positive human sera tested reacted with the carboxy-terminal third of the integrase protein. Furthermore, they crossreacted with the same part of the heterologous protein. Half (50%) of the HIV-1/integrase-positive sera additionally detected antigenic epitopes in the amino-terminal third of the HIV-1 protein. Two of the recombinant proteins were used to generate polyclonal rabbit sera, which react with type-common epitopes of both integrase proteins. To map the B-cell epitopes of the HIV integrase proteins in more detail, overlapping decapeptides representing the entire integrase proteins of HIV-1 and HIV-2 were synthesized and used in a pin-based oligopeptide ELISA to scan human sera. This method can define three potential immunogenic epitopes of the HIV-1 integrase and one potential epitope of the HIV-2 integrase. The immunodominant epitopes of the HIV-1 integrase, one localized in the amino-terminal (IDKAQDEHEKYHSNWRAM), one in the central (QMAVFIHNFKRKGGIGGY), and one in the carboxy-terminal (AVVIQDNSDIKVVPRRK) part of the protein were synthesized as oligopeptides and used to test a larger panel of human sera in ELISA (156 HIV-1+ sera and 104 HIV-1- sera). The amino- and the carboxy-terminal epitopes were of equivalent reactivity, while the central part of the HIV-1 integrase seems to be less immunogenic. Nearly 90% of the HIV-1/integrase-positive human sera could be detected by a combination of these three peptides.