title: Lysis of cells infected with HIV-1 by human lymphocytes targeted with monoclonal antibody heteroconjugates.
abstract: The present study was undertaken to determine whether human PBL can be specifically focused to lyse cells infected with HIV-1 by mAb heteroconjugates that can bridge target and effector cells. A mAb directed against the central portion of HIV-1 glycoprotein gp110 was chemically cross-linked to a mAb directed against the CD3/TCR complex or to a mAb directed against the CD16 Fc gamma-R expressed on large granular lymphocytes (LGL). HIV-1-infected cells, but not uninfected cells, were found to be lysed to a greater extent by PBL in the presence of the gp110 X CD3 or the gp110 X CD16 antibody heteroconjugate than in the presence of the single antibodies or a mixture of the mAb comprising the heteroconjugates. Pretreatment of PBL with anti-CD3 or IL-2 augments their ability to lyse HIV-1-infected cells in the presence of the heteroconjugates. Lysis by anti-CD3-activated PBL in the presence of the gp110 X CD3 heteroconjugate was found to be mediated by CD8+-enriched T cells, whereas lysis by IL-2-treated PBL in the presence of the gp110 X CD16 heteroconjugate is mediated by PBL enriched for CD16+ cells, which are primarily LGL. Furthermore, PBL from asymptomatic, HIV-1-infected seropositive donors were found to be functional in lysing HIV-1-infected cells in the presence of the antibody heteroconjugates. Such antibody heteroconjugates, which can target T cells or LGL to lyse HIV-1-infected cells, may be of prophylactic or therapeutic value in HIV-1-infected individuals.
authors.affiliation: Oncogen, Seattle, WA 98121.
authors.forename: J M
authors.initials: JM
authors.lastname: Zarling
authors.forename: P A
authors.initials: PA
authors.lastname: Moran
authors.forename: L S
authors.initials: LS
authors.lastname: Grosmaire
authors.forename: J
authors.initials: J
authors.lastname: McClure
authors.forename: K
authors.initials: K
authors.lastname: Shriver
authors.forename: J A
authors.initials: JA
authors.lastname: Ledbetter
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies; D015488:HIV Antigens; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG; D012191:Retroviridae Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015483:HIV Antibodies; D015488:HIV Antigens; D007376:Interleukin-2; D011961:Receptors, Fc; D017452:Receptors, IgG; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; C055004:gp 110 env protein, Human immunodeficiency virus