HIV neutralizing IgA in exposed seronegative subjects recognise an epitopewithin the gp41 coiled-coil pocket

Human immunodeficiency virus (HIV)-specific IgA can be detected in cervical secretions, saliva, and sera of HIV-infected and HIV-uninfected individual s with a known exposure to the virus. IgA from HIV-uninfected exposed seron egative individuals (ESN) neutralize in vitro primary strains of HIV-1. We analyzed the epitopes of HIV recognized by serum HIV-specific IgA of ESN in dividuals to identify the antigenic correlates of HIV neutralization in exp osed-uninfected subjects, and to verify whether different epitopes would be recognized by HIV-specific IgA of ESN and of HIV-infected patients. Result s confirmed that HIV-neutralizing IgA are detected in sera of ESN and showe d that neutralization of primary HIV strains is mediated by the recognition of different epitopes in HIV-infected patients and ESN. Thus, whereas IgA of HIV+ individuals recognize epitopes expressed both within gp120 and gp41 , IgA of ESN exclusively bind to gp41-expressed epitopes. Epitope mapping r evealed that the epitope recognized by serum IgA of ESN on gp41 is restrict ed to aa 581-584 (LQAR) and corresponds to coiled coil pocket in the alpha helic region. In contrast, the epitope seen by IgA of HIV-infected patients on gp41 is identified by two regions; the first is contained within the cy stein loop (aa 589-618), the second correspond to C terminal region in the extra membrane region of gp 41 (aa 642-673). Thus, we have identified and c haracterized the epitopes that mediate neutralization of HIV in individuals in whom infection does not occur despite multiple exposures to the virus. These results have important implications for the development of a new ther apy against HIV infection.