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Stimulation of Antiviral Antibody Response in SHIV-IIIB-Infected Macaques (2001)

Muller, S. ; Margolin, D. H. ; Min, G. ; [et al.]

Oxford, UK : Blackwell Science Ltd

Scandinavian journal of immunology 54 (2001), S. 0

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ISSN: 1365-3083

Source: Blackwell Publishing Journal Backfiles 1879-2005

Topics: Medicine

Notes: Three macaques infected with SHIV-IIIB and expressing the shared 1F7-idiotypic marker on antibodies against HIV-1 gp120, were injected intravenously with 1F7 monoclonal antibodies (MoAb). As controls, a SHIV-IIIB-infected macaque was injected with a HIV-unrelated mouse monoclonal isotype antibody (TEPC-183) and two healthy, noninfected macaques were injected with MoAb 1F7. 1F7-id-expressing antibodies against gp120-IIIB decreased in two of the three MoAb 1F7-treated macaques and then rebounded. Importantly, antibodies binding to envelope proteins of heterologous HIV-1 strains MN, CM, and SF2, which were low or not detectable before the MoAb 1F7 treatment, increased rapidly following MoAb inoculations in all three 1F7 MoAb treated macaques, but not in the macaque injected with control MoAb TEPC-183. Newly arising antibodies reacting with heterologous virus, i.e. HIV-1 gp120-MN, SF2, and CM did not express 1F7-id. Surprisingly, significant increases of antibodies were also observed in the 1F7-inoculated macaques' antibodies directed to non-HIV antigens (DNP, peptides and BSA). The noninfected control animals did not produce antibodies to these antigens despite MoAb 1F7 treatment. These data show that the MoAb 1F7 injections of chronically SHIV-IIIB-infected macaques resulted in idiotype-specific clonal suppression with broadening the antibody response to HIV envelope proteins.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1046/j.1365-3083.2001.00982.x

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Germline repertoire of the immunoglobulin V H 3 family in rhesus monkeys (2000)

Helmuth, Erika F. ; Letvin, Norman L. ; Margolin, D. H.

Springer

Immunogenetics 51 (2000), S. 519-527

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ISSN: 1432-1211

Keywords: Key words Immunoglobulins ; Nonhuman primates ; VH3

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine

Notes: Abstract To facilitate molecular studies of antibody responses in rhesus monkeys (Macaca mulatta), we cloned and sequenced germline segments from its largest and most diverse immunoglobulin heavy-chain gene family, V H 3. Using a PCR-based approach, we characterized 29 sequences, 20 with open reading frames (ORFs) and 9 pseudogenes. The leader sequences, introns, exons, and recombination signal sequences of M. mulatta V H 3 gene segments are not strictly identical to those of humans, but the mature coding regions demonstrate, on average, greater than 90% sequence similarity. Although the framework regions are more highly conserved, the complementarity-determining regions (CDRs) also show strong similarities, and their predicted three-dimensional structures resemble those of their human homologues. In one instance, homologous macaque and human CDR1 sequences were 100% identical at the nucleotide level, and some CDR2s shared nucleotide identity as high as 96.5%. However, some rhesus V H 3 ORFs have unusual structural features, including atypical CDR lengths and uncommon amino acids at structurally crucial positions. The similarity of rhesus and human V H 3 homologues reinforces the notion that humoral immunity in this nonhuman primate species is an appropriate system for modeling human antibody responses.