Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains.
Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the beta 19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies.
Xiang
Shi-Hua
SH
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Wang
Liping
L
Abreu
Mariam
M
Huang
Chih-Chin
CC
Kwong
Peter D
PD
Rosenberg
Eric
E
Robinson
James E
JE
Sodroski
Joseph
J
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D009500:Neutralization Tests; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism; D015728:Receptors, HIV / Q000737:chemistry / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D015728:Receptors, HIV