Complement-mediated anti-HIV-1 effect induced by human IgM monoclonal antibody against ganglioside GM2.
HIV-infected cells aberrantly express a high level of antigenic glycosidic structures such as GM2 and Gg4. Some normal sera containing natural IgM Abs to GM2 and/or Gg4 cause C-mediated cytolysis of HIV-infected cells. In the present study we demonstrated that a human IgM anti-GM2 mAb (L55 Ab) can induce cytolysis of HIV-infected cells. Increased GM2 expression by HIV-1 infection of a human T cell line (MOLT4), a human monocyte cell line (U937), and human lymphoblastoid cells was confirmed by immunofluorescence staining with L55 Ab. These infected cells were readily lysed by L55 Ab in the presence of fresh human serum as a C source that alone did not cause cytolysis. L55 Ab also had the ability to destroy HIV-1 particles via C-mediated lysis. By adding L55 Ab together with human C to mixed culture of HIV-infected cells and naive cells, HIV-1 replication was significantly suppressed, and this effect was synergistic when L55 Ab was combined with a reverse transcriptase inhibitor and a proteinase inhibitor. Therefore, a human IgM anti-GM2 mAb may be effective in treating HIV-infected patients, especially when used together with chemotherapeutic agents.
Wu
X
X
Department of Molecular Biology, Nagoya City University School of Medicine, Japan.
Okada
N
N
Momota
H
H
Irie
R F
RF
Okada
H
H
D019380:Anti-HIV Agents / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000633:toxicity; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D003165:Complement System Proteins / Q000502:physiology*; D003602:Cytotoxicity, Immunologic; D005678:G(M2) Ganglioside / Q000096:biosynthesis / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology* / Q000633:toxicity; D015459:Leukemia-Lymphoma, Adult T-Cell; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D014771:Virion / Q000276:immunology; D014779:Virus Replication
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D005678:G(M2) Ganglioside; D003165:Complement System Proteins