Characterization of gp120 hydrolysis by IgA antibodies from humans without HIV infection.
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.
Planque
Stephanie
S
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.
Mitsuda
Yukie
Y
Taguchi
Hiroaki
H
Salas
Maria
M
Morris
Mary-Kate
MK
Nishiyama
Yasuhiro
Y
Kyle
Robert
R
Okhuysen
Pablo
P
Escobar
Miguel
M
Hunter
Robert
R
Sheppard
Haynes W
HW
Hanson
Carl
C
Paul
Sudhir
S
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
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D006241:Haptens; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G