High levels of antibodies to the CD4 binding domain of human immunodeficiency virus type 1 glycoprotein 120 are associated with faster disease progression.
Human monoclonal antibodies (Abs) to the CD4 binding domain of human immunodeficiency virus (HIV) type 1 glycoprotein (gp) 120 (gp120(CD4bd)) inhibit gp120 presentation to gp120-specific T helper (Th) cells. Since Th responses are critical to control HIV, anti-gp120(CD4bd) Abs could be involved in HIV pathogenesis. Therefore, anti-gp120(CD4bd) Ab levels were compared in serum samples from matched pairs of HIV-positive rapid progressors (RPs) and slow progressors (SPs). Many RPs had higher levels of anti-gp120(CD4bd) Abs than their corresponding SPs. However, Ab levels to whole gp120 and to its C5 domain were similar. Hence, the higher levels of anti-gp120(CD4bd) Abs detected in the serum of RPs do not reflect generalized increases in Ab levels to whole gp120. Moreover, anti-gp120(CD4bd) Ab levels correlated with the amount of inhibition of gp120-specific Th proliferation in the presence of respective serum immunoglobulin G. These findings document a novel mechanism of HIV pathogenesis mediated by anti-gp120(CD4bd) Abs exhibiting suppressive activity on gp120 presentation.
Department of Pathology, New York University School of Medicine, and Veterans Affairs New York Harbor Healthcare System, New York, New York, USA.
Peter C
PC
Chien
Sandra
S
Cohen
Cynthia
C
Kleeberger
Janis
J
Giorgi
John
J
Phair
Susan
S
Zolla-Pazner
Catarina E
CE
Hioe
D001665:Binding Sites; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D017434:Protein Structure, Tertiary; D012189:Retrospective Studies
D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120