Two new human monoclonal antibodies against HIV type 1 glycoprotein 120: characterization and neutralizing activities against HIV type 1 strains.
Two human IgGk monoclonal antibodies (HuMAbs), termed 48-16 and 50-61A, were derived by Epstein-Barr virus transformation of B cells from two HIV-1-infected donors. These HuMAbs recognized discrete, nonoverlapping, and conformational or discontinuous epitopes on the gp120 envelope protein of HIV-1. The binding affinities of 48-16 and 50-61A for recombinant gp120 from HIV-1LAI strain, reflected by their dissociation constants, were estimated to be 2-5 x 10(-9) and 2.4 x 10(-10) M, respectively. 48-16 was shown to react with a conserved determinant present on a variety of divergent laboratory isolates, residing outside the CD4-binding site and the V3 region, which remains to be determined. 48-16 did not display, however, any detectable functional activity. 50-61A exhibited a more restricted recognition pattern, but was able to completely inhibit the 2 HIV-1 laboratory strains LAI and SF2 in a concentration range of 0.5-10 micrograms/ml, as measured by an antigen capture assay. The ability of 50-61A to block the interaction between recombinant gp120LAI and recombinant as well as cellular CD4 indicated that 50-61A epitope was localized near or within the CD4-binding side. We also demonstrated that 50-61A- and 48-16-defined epitopes (or closely related epitopes) were immunogenic in infected humans, since serum samples from 45 seropositive subjects were able to inhibit both gp120LAI-HuMAb recognitions. However, the presence of "50-61A-like" antibodies in these sera could not be associated with their neutralizing activities of HIV-1LAI infection. Interest in producing such antibodies for characterization of the human B cell repertoire to HIV-1 and their potential use in passive immunotherapy or vaccination strategy against AIDS are discussed.
Février
M
M
Unité d'Immunogénétique Cellulaire, Institut Pasteur, Paris, France.
Boudet
F
F
Deslandres
A
A
Theze
J
J
D000911:Antibodies, Monoclonal; D000915:Antibody Affinity; D001665:Binding Sites; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G; D009500:Neutralization Tests
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G