nd human Iymphocytes, a highly conserved region (aa583-599; LQARILAV-ERYLKDQQL) was identified in gp41 as a binding site for human T cells and monocytes1-3, Gp41 could thus inhibit lym-phocyte proliferation4 and upregulate major histocompatibility complex (MHC) class I, class II and intercellular adhesion molecule 1 (ICAM-1) expression5-effects similar to those of human type I interferons. When we compared the sequences of gp41 and type I interferons, a similar epi-tope RILAV--YLKD was found in the im-munosuppressive domain (ISD) of gp41 and two regions in interferon α(IFN-α) (aa29-35 and 113-129), IFN-β(aa31-27 and 125-138) and IFN-ω(aa29-35 and 123-136) (Fig.1). Surprisingly, the common epitope exists within the receptor binding sites of gp41, IFN-α and IFN-β(Ref.6.) We characterized the common epitope and found increased levels of antibodies to IFN-αand IFN-βin20 HIV-infectedindividuals, compared with levels in normal healthy controls; these lev-els subsequently decreased with disease progression. Affinity-purified anti--gp41 an-tibody from HIV-infected individduals was shown to recognize human IFN-αand IFN-β. In addition, anti-IFN-αand IFN-β antibodies interacted with gp41 and its peptide(aa583-599), and inhibited gp41 binding to human lymphocytes. These results suggest that the common immunological epitope within gp41 induces incrased levels of an-tibodies that can interact with IFN-αand IFN-β. Gringeri et al. demonstrated that HIV-infected patients treated with an IFN-α vac-cine showed a significant reduction in the rate of disease progression, which was asso-ciated with an increase in IFN-αantibody titer and an increase in IFN-α-neutralizing capacity. The anti-IFN-α antibody was shown to recognize aa560-599 of HIV-1 gp41 (Ref. 7). These data suggest that the common immunological epitope within re-ceptor binding sites may be associated with protetive activity. Interestingly, a similar epitope in SIV gp32 could protect macaques from SIV infection89, indication that the common immunological epitope on gp41, IFN-αand IFN-β could be useful in the de-velopment of a vaccine strategy against HIV-infection.