AUTOANTIBODIES TO CD4 IN HIV TYPE 1-EXPOSED SERONEGATIVE INDIVIDUALS

The aim of this study was to investigate the presence and the fine spe cificity of anti-CD4 autoantibodies in seronegative subjects sexually exposed to HIV-1. Anti-CD4 autoantibodies were previously detected in a fraction of HIV-1-seropositive individuals, Whole sera, purified IgG fractions, and supernatants of EBV-transformed lymphoblastoid cell li nes were analyzed by means of ELISA, Western blot, and by competition assays using monoclonal antibodies with known fine specificities. Anti -CD4 antibodies were found in 6 of 18 individuals exposed to HIV-1 inf ection and who have been persistently seronegative. These antibodies i nhibited HIV-1-driven syncytium formation, did not interfere with the CD4-gp120 interaction, and competed for CD4 binding with two of three anti-CD4 monoclonals with known fine specificities. Moreover, autoanti bodies with the same fine specificities were found in the supernatants of oligoclonal EBV-transformed B cell lines derived from these indivi duals, At variance, in the HIV-1-positive patients included in our stu dy, the anti-CD4 antibody response was directed to a broader panel of epitopes, including those involved in CD4-gp120 interactions. In concl usion, anti-CD4 antibodies specific for defined epitopes of the CD4 mo lecule are generated in the course of an early immune response to HIV- 1 antigens in the absence of other signs of infection, as they can be detected by conventional methods, These autoantibodies may play a prot ective role either alone or in association with other cellular and hum oral factors.