Enhanced endocytosis and anti-human immunodeficiency virus type 1 activity of anti-rev antibodies after cationization.
Transmembrane transport and endocytosis of antibodies is facilitated by cationization, when the isoelectric point of the antibody is raised to the cationic range. The present studies describe the preparation of affinity-purified polyclonal antibodies directed against a 16-amino acid synthetic peptide corresponding to amino acids 35-50 of the 116-amino acid rev protein of human immunodeficiency virus type 1 (HIV-1). The concentration of cationized anti-rev35-50 antibody that results in 50% binding to the rev epitope, based on results with an immunoradiometric assay, also results in a statistically significant 37% inhibition of HIV-1 replication in human peripheral blood lymphocytes. The cationized antibodies caused no measurable toxicity to the cells, on the basis of [3H]thymidine incorporation. These studies demonstrate that cationization results in enhanced endocytosis of the antibody and enhanced inhibition of HIV-1 replication, consistent with intracellular immunization of the rev protein.
Pardridge
W M
WM
Department of Medicine, UCLA School of Medicine 90024.
Bickel
U
U
Buciak
J
J
Yang
J
J
Diagne
A
A
D000595:Amino Acid Sequence; D002412:Cations; D002478:Cells, Cultured; D004705:Endocytosis / Q000276:immunology*; D015694:Gene Products, rev / Q000737:chemistry / Q000276:immunology*; D015757:Genes, rev; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000096:biosynthesis / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015592:Immunoradiometric Assay; D007525:Isoelectric Focusing; D007526:Isoelectric Point; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011863:Radioimmunoassay; D013696:Temperature; D014779:Virus Replication / Q000276:immunology; D054321:rev Gene Products, Human Immunodeficiency Virus
D002412:Cations; D015694:Gene Products, rev; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D010446:Peptide Fragments; D054321:rev Gene Products, Human Immunodeficiency Virus