Identification of B-cell antigenic sites on HIV-2 gp125.
Synthetic peptides were used to identify continuous antigenic sites on the external envelope glycoprotein gp125 of human immunodeficiency virus (HIV)-2. Initially, seven HIV-2-positive human serum samples were screened with 172 sequential nonapeptides containing a six-amino-acid overlap. This represents the entire gp125 molecule of HIV-2ISY. The antibody reactivity was found to be mainly restricted to 14 regions within gp125. Following these results, 33 longer peptides, 15-24 amino acids in length, were synthesized and tested against a larger number of samples. Eleven antigenic regions were thus identified. Two of these were detected within a region corresponding to the C1 region and four others within a region corresponding to the C2 region of HIV-1. The highest frequency of reactivity (90%) of 31 HIV-2 seropositive human serum samples was elicited by three peptides from a region corresponding to the V3 region of HIV-1. The C-terminal portion of this region was recognized by almost 80% of the samples. Reactive regions corresponding to the V4, V5, and N-terminal portion of V4 were also identified. A mouse monoclonal antibody reacting with gp125 was mapped to the N-terminal region of the molecule and was found to react with the sequence DVWNLFETS. The peptides were used to evaluate the antibody response of monkeys immunized with whole killed HIV-2 or simian immunodeficiency virus (SIV). The monkeys showed a pattern of reactivity similar to HIV-2-infected human serum samples. Postinfection samples from monkeys inoculated with HIV-2 or SIV reacted mainly to peptides from the V3 region. Two peptides were used to detect the seroconversion of two SIV-infected monkeys. Thus, we have demonstrated that human seroreactivity to HIV-2 gp125 occurs at a few distinct linear antigenic sites distributed at similar positions on the molecule as those in HIV-1 gp120.
Department of Virology, National Bacteriological Laboratory, Stockholm, Sweden.
M
M
Mannervik
P
P
Putkonen
U
U
Rudén
K A
KA
Kent
E
E
Norrby
B
B
Wahren
P A
PA
Broliden
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D008252:Macaca fascicularis; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D010455:Peptides; D011498:Protein Precursors; D054299:env Gene Products, Human Immunodeficiency Virus; C066316:gp125 envelope protein, Human immunodeficiency virus 2