Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120.
Sulfated tyrosines at the amino terminus of the principal HIV-1 coreceptor CCR5 play a critical role in its ability to bind the HIV-1 envelope glycoprotein gp120 and mediate HIV-1 infection. Here, we show that a number of human antibodies directed against gp120 are tyrosine sulfated at their antigen binding sites. Like that of CCR5, antibody association with gp120 is dependent on sulfate moieties, enhanced by CD4, and inhibited by sulfated CCR5-derived peptides. Most of these antibodies preferentially associate with gp120 molecules of CCR5-utilizing (R5) isolates and neutralize primary R5 isolates more efficiently than laboratory-adapted isolates. These studies identify a distinct subset of CD4-induced HIV-1 neutralizing antibodies that closely emulate CCR5 and demonstrate that tyrosine sulfation can contribute to the potency and diversity of the human humoral response.
Choe
Hyeryun
H
Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Li
Wenhui
W
Wright
Paulette L
PL
Vasilieva
Natalya
N
Venturi
Miro
M
Huang
Chih-Chin
CC
Grundner
Christoph
C
Dorfman
Tatyana
T
Zwick
Michael B
MB
Wang
Liping
L
Rosenberg
Eric S
ES
Kwong
Peter D
PD
Burton
Dennis R
DR
Robinson
James E
JE
Sodroski
Joseph G
JG
Farzan
Michael
M
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D013431:Sulfates; D014443:Tyrosine