Immunodominant epitope regions of HIV-1 reverse transcriptase: correlations with HIV-1+ serum IgG inhibitory to polymerase activity and with disease progression.
Anti-HIV-1 polymerase antibodies are present in high titer throughout the course of HIV disease. The possibility that a subset of these immunoglobulins might represent an adaptive immune response was suggested by several studies, from this laboratory and others, identifying IgGs capable of inhibiting the catalytic activity of reverse transcriptase (RT) in asymptomatic HIV+ individuals, which were absent from most AIDS patients. We have now determined the dominant B-cell epitope segments of RT recognized during natural HIV-1 infection, with one epitope region, amino acids 244-269, recognized by the majority of HIV-1 positive sera. We have also correlated IgG RT inhibitor activity with amino acids 157-178, corresponding to sequences previously identified by monoclonal antibody mapping and site-directed mutagenesis as necessary for the maintenance of polymerase function. Absence of reactivity to synthetic peptides prepared from this latter region correlated with both advanced HIV disease in a cross-sectional survey of 57 HIV-1+ individuals, and progression of clinical symptoms in a small cohort followed longitudinally. Given current interest in examining diverse components of HIV in development of peptide-based protective vaccines and specific active immunotherapies, these segments of RT might be considered as potential candidates.
Grimison
B
B
Department of Medicine, Cornell University Medical College, New York, New York 10021, USA.
Laurence
J
J
D000595:Amino Acid Sequence; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis* / Q000737:chemistry; D007074:Immunoglobulin G / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry / Q000276:immunology*; D018894:Reverse Transcriptase Inhibitors
D015483:HIV Antibodies; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase