Human immunodeficiency virus type 1 evades T-helper responses by exploiting antibodies that suppress antigen processing.
T-helper responses are important for controlling chronic viral infections, yet T-helper responses specific to human immunodeficiency virus type 1 (HIV-1), particularly to envelope glycoproteins, are lacking in the vast majority of HIV-infected individuals. It was previously shown that the presence of antibodies to the CD4-binding domain (CD4bd) of HIV-1 glycoprotein 120 (gp120) prevents T-helper responses to gp120, but their suppressive mechanisms were undefined (C. E. Hioe et al., J. Virol. 75:10950-10957, 2001). The present study demonstrates that gp120, when complexed to anti-CD4bd antibodies, becomes more resistant to proteolysis by lysosomal enzymes from antigen-presenting cells such that peptide epitopes are not released and presented efficiently by major histocompatibility complex class II molecules to gp120-specific CD4 T cells. Antibodies to other gp120 regions do not confer this effect. Thus, HIV may evade anti-viral T-helper responses by inducing and exploiting antibodies that conceal the virus envelope antigens from T cells.
Chien
Peter C
PC
Department of Pathology, New York University School of Medicine and Veterans Affairs, New York Harbor Healthcare System, New York, NY 10010, USA.
Cohen
Sandra
S
Tuen
Michael
M
Arthos
James
J
Chen
Pei-de
PD
Patel
Sukeshi
S
Hioe
Catarina E
CE
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000201:enzymology; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120