INTERNALIZATION OF ANTI-GP120 MONOCLONAL-ANTIBODY AND HUMAN-ANTIBODIES BY HIV-1-INFECTED T-LYMPHOCYTES

A high affinity, neutralizing monoclonal antibody (MAb), 5023, develop ed against a synthetic peptide representing amino acid residues 308-32 2 of the V3 loop of human immunodeficiency virus type 1 (HIV-1)IIIB en velope protein, gp120, was found to be internalized efficiently by HIV -1IIIB (HXB-2 isolate) infected T lymphocytes at the time of syncytia formation. Another MAb (5025) developed against the same peptide was i nternalized poorly, and two other MAb against gp120 amino acid residue s, 307-328 and 308-332, were not internalized. The internalized MAb 50 23 was localized in the cytoplasm and the nucleus. MAb 5023 was not in ternalized by noninfected T lymphocytes, even though it cross-reacted with a 24,000-M(r) protein expressed by several T lymphocyte cell line s. MAb 5023, conjugated with ricin A, exerted a cytotoxic effect on HI V-1-infected cells. We suggest that MAb 5023 is able to penetrate HIV- infected cells and therefore may be used to deliver toxins and/or othe r therapeutic agents into the infected cells. A fraction of HIV-neutra lizing human antibodies to nonglycosylated gp120 SF2 (env 2-3) was als o found to penetrate HIV-1 HXB-2-infected cells. It is possible that a ntibodies able to enter the infected cells may inhibit expression of g p120 and assembly of the virion inside the cell. Internalized antibodi es, synthesized during natural human infection, may protect the patien ts more effectively than antibodies able to interact with the virus pr ior to infection.