Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals.
Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies. To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.
Scheid
Johannes F
JF
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10065, USA.
Mouquet
Hugo
H
Feldhahn
Niklas
N
Seaman
Michael S
MS
Velinzon
Klara
K
Pietzsch
John
J
Ott
Rene G
RG
Anthony
Robert M
RM
Zebroski
Henry
H
Hurley
Arlene
A
Phogat
Adhuna
A
Chakrabarti
Bimal
B
Li
Yuxing
Y
Connors
Mark
M
Pereyra
Florencia
F
Walker
Bruce D
BD
Wardemann
Hedda
H
Ho
David
D
Wyatt
Richard T
RT
Mascola
John R
JR
Ravetch
Jeffrey V
JV
Nussenzweig
Michel C
MC
D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D015483:HIV Antibodies / Q000032:analysis* / Q000276:immunology* / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D009500:Neutralization Tests; D015728:Receptors, HIV / Q000378:metabolism; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1