HLA homology within the C5 domain promotes peptide binding by HIV type 1 gp120.
The mechanisms by which HIV-1 induces chronic pathogenic immune activation associated with disease progression remain unclear despite many years of AIDS research. One proposal suggests that sequence and structural mimicry between gp120 and HLA may endow HIV with the capacity to arouse alloreactive and autoimmune responses within the susceptible host, fueling disease progression in a manner similar to graft-versus-host disease (GVHD). Both gp120 and HLA share a common functional interaction with CD4 but also demonstrate peptide binding properties. Here we report the conserved nature of this feature across HIV-1 envelopes, the crucial role of the HLA homologous C5 region for peptide interactions, and the elimination of this property through specific antibody targeting. Given that the C5 domain mimics a HLA activation domain and the reported clinical benefits associated with nonneutralizing antibodies against this region, targeting the C5 domain may have use as a therapeutic vaccine to protect against disease progression.
Cadogan
Martin
M
Department of Cellular and Molecular Medicine, St. George's University of London, London SW17 0RE, UK.
Austen
Brian
B
Heeney
Jonathan L
JL
Dalgleish
Angus G
AG
D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015483:HIV Antibodies / Q000276:immunology / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology* / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008958:Models, Molecular; D018716:Molecular Mimicry; D054730:Protein Interaction Domains and Motifs; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015789:HLA-A2 Antigen; D015798:HLA-DR1 Antigen; C514793:gp120 protein, Human immunodeficiency virus 1