title: Characterization of gp120 hydrolysis by IgA antibodies from humans without HIV infection.
abstract: Antibody hydrolysis of the superantigenic gp120 site and HIV-1 neutralization was studied as a potential anti-HIV mechanism in uninfected humans. gp120 hydrolysis by purified serum and salivary antibodies was determined by electrophoresis and peptide sequencing, the proteolytic mechanism was analyzed using electrophilic peptide analogs, and viral neutralization was studied using peripheral blood mononuclear cells as hosts. Polyclonal and monoclonal IgA but not IgG preparations selectively catalyzed the cleavage of HIV gp120 at rates sufficient to predict biologically relevant protection against the virus. The IgA hydrolytic reaction proceeded by noncovalent recognition of gp120 residues 421-433, a component of the superantigenic site of gp120, coordinated with peptide bond cleavage via a serine protease-like mechanism. The Lys-432-Ala-433 bond was one of the cleavage sites. Infection of peripheral blood mononuclear cells by a primary isolate of HIV was neutralized by the IgA but not IgG fractions. The neutralizing activity was specifically inhibited by an electrophilic inhibitor of the catalytic activity. The existence of catalytic IgAs to gp120 in uninfected humans suggests their role in resistance to HIV.
authors.affiliation: Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine and Hemophilia and Thrombophilia Center, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Planque
authors.forename: Yukie
authors.initials: Y
authors.lastname: Mitsuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taguchi
authors.forename: Maria
authors.initials: M
authors.lastname: Salas
authors.forename: Mary-Kate
authors.initials: MK
authors.lastname: Morris
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Robert
authors.initials: R
authors.lastname: Kyle
authors.forename: Pablo
authors.initials: P
authors.lastname: Okhuysen
authors.forename: Miguel
authors.initials: M
authors.lastname: Escobar
authors.forename: Robert
authors.initials: R
authors.lastname: Hunter
authors.forename: Haynes W
authors.initials: HW
authors.lastname: Sheppard
authors.forename: Carl
authors.initials: C
authors.lastname: Hanson
authors.forename: Sudhir
authors.initials: S
authors.lastname: Paul
mesh_terms: D000328:Adult; D017151:Antibodies, Catalytic / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006241:Haptens / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008297:Male; D009500:Neutralization Tests
chemical_list: D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D006241:Haptens; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G