THE HIV-1 NEF PROTEIN SHARES AN ANTIGENIC DETERMINANT WITH A T-CELL SURFACE PROTEIN

Objective: To characterize antigens on uninfected T lymphocytes reactive with monoclonal antibodies (MAb) directed against the HIV-1 Nef protein, and to search for antibodies directed against this epitope in HIV-1-infected individuals. Design: Murine MAb directed against an epitope of Nef defined by amino acids 60-73 reacted with cell surface antigens of normal peripheral blood lymphocytes and permanent human T-cell lines. Methods: The specificity of the MAb reaction was investigated by flow cytometry and immunofluorescence. The antigen was precipitated from lysates or uninfected cells using MAb or sera from HIV-1-infected individuals and analysed by Western blot and isoelectrofocusing. Results: An antigen with an apparent relative molecular mass of 137000 and an isoelectric point of 8.45 was immunoprecipitated with the cross-reactive MAb from uninfected human T cells. Sera from HIV-positive individuals recognizing a Nef epitope partially overlapping with the binding site of the cross-reactive MAb stained the 137 kD protein precipitated with the MAb in Western blot analysis, while HIV-positive sera without antibodies to this Nef region and sera from uninfected individuals were negative. Conclusion: The induction of autoantibodies cross-reactive with cellular surface proteins may play a role in the pathogenesis of AIDS.