IgG Fc Receptor III Homologues in Nonhuman Primate Species: Genetic Characterization and Ligand Interactions

Rogers, Kenneth A.; Scinicariello, Franco; Attanasio, Roberta

doi:10.4049/jimmunol.177.6.3848

Cited by 88 publications

(75 citation statements)

References 59 publications

(57 reference statements)

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“…DNA was extracted from PBMCs using the DNeasy blood and tissue kit (Qiagen, Valencia, CA) and subjected to different PCRs, using primers and conditions as described previously (56). Exons 1 and 2 were each amplified as single PCR amplicons; exons 3 and 4 were each amplified in two overlapping fragments; the coding region and partial 3Ј untranslated region of exon 5 were amplified in a single amplicon using seminested primers, as described previously (56).…”

Section: Methodsmentioning

confidence: 99%

Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host

Gaufin

Pattison

Gautam

et al. 2009

J Virol

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Simian immunodeficiency virus (SIV)-infected African nonhuman primates do not progress to AIDS in spite of high and persistent viral loads (VLs). Some authors consider the high viral replication observed in chronic natural SIV infections to be due to lower anti-SIV antibody titers than those in rhesus macaques, suggesting a role of antibodies in controlling viral replication. We therefore investigated the impact of antibody responses on the outcome of acute and chronic SIVagm replication in African green monkeys (AGMs). Nine AGMs were infected with SIVagm.sab. Four AGMs were infused with 50 mg/kg of body weight anti-CD20 (rituximab; a gift from Genentech) every 21 days, starting from day ؊7 postinfection up to 184 days. The remaining AGMs were used as controls and received SIVagm only. Rituximab-treated AGMs were successfully depleted of CD20 cells in peripheral blood, lymph nodes (LNs), and intestine, as shown by the dynamics of CD20 ؉ and CD79a ؉ cells. There was no significant difference in VLs between CD20-depleted AGMs and control monkeys: peak VLs ranged from 10 7 to 10 8 copies/ml; set-point values were 10 4 to 10 5 SIV RNA copies/ml. Levels of acute mucosal CD4 ؉ T-cell depletion were similar for treated and nontreated animals. SIVagm seroconversion was delayed for the CD20-depleted AGMs compared to results for the controls. There was a significant difference in both the timing and magnitude of neutralizing antibody responses for CD20-depleted AGMs compared to results for controls. CD20 depletion significantly altered the histological structure of the germinal centers in the LNs and Peyer's patches. Our results, although obtained with a limited number of animals, suggest that humoral immune responses play only a minor role in the control of SIV viral replication during acute and chronic SIV infection in natural hosts.

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Section: Methodsmentioning

confidence: 99%

Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host

Gaufin

Pattison

Gautam

et al. 2009

J Virol

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“…Indeed, it is widely recognized that the characterization of NHP Ab molecules is still incomplete. Results from recent studies (8) indicate that, although NHP and human Ab molecules are very similar to each other, there are several differences that might lead to the incorrect interpretation of results from studies performed in these species.…”

mentioning

confidence: 89%

“…Recombinant NHP CD16 binds to human IgG subclasses different from those bound by human CD16, despite a nearly complete conservation of residues known to be involved in ligand binding (8). Because of its major role in mucosal and systemic immunity, and because of the possible therapeutic potential in modulating the IgA/CD89 interactions (29), IgA is an Ab class that requires full characterization in NHP species.…”

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confidence: 99%

Nonhuman Primate IgA: Genetic Heterogeneity and Interactions with CD89

Rogers

Jayashankar

Scinicariello

et al. 2008

The Journal of Immunology

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Nonhuman primates are extremely valuable animal models for a variety of human diseases. However, it is now becoming evident that these models, although widely used, are still uncharacterized. The major role that nonhuman primate species play in AIDS research as well as in the testing of Ab-based therapeutics requires the full characterization of structure and function of their Ab molecules. IgA is the Ab class mostly involved in protection at mucosal surfaces. By binding to its specific Fc receptor CD89, IgA plays additional and poorly understood roles in immunity. Therefore, Ig heavy α (IGHA) constant (C) genes were cloned and sequenced in four different species (rhesus macaques, pig-tailed macaques, baboons, and sooty mangabeys). Sequence analysis confirmed the high degree of intraspecies polymorphism present in nonhuman primates. Individual animals were either homozygous or heterozygous for IGHA genes. Highly variable hinge regions were shared by animals of different geographic origins and were present in different combinations in heterozygous animals. Therefore, it appears that although highly heterogeneous, hinge sequences are present only in limited numbers in various nonhuman primate populations. A macaque recombinant IgA molecule was generated and used to assess its interaction with a recombinant macaque CD89. Macaque CD89 was able to bind its native ligand as well as human IgA1 and IgA2. Presence of Ag enhanced macaque IgA binding and blocking of macaque CD89 N-glycosylation reduced CD89 expression. Together, our results suggest that, despite the presence of IgA polymorphism, nonhuman primates appear suitable for studies that involve the IgA/CD89 system.

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“…However it should also be noted that despite much similarity there are potentially important differences in diversity, genetics, and biology of antibody and of FcRs in macaques compared to humans which are mentioned below and in [29][30][31][32][33]. Thus, the extrapolation of FcγR-mediated antibody functions from these models to efficacy in humans should be made with caution.…”

Section: Introductionmentioning

confidence: 99%

Antibody functional assays as measures of Fc receptor-mediated immunity to HIV - new technologies and their impact on the HIV vaccine field.

Wines¹,

Billings²,

Mcleand³

et al. 2017

CHR

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Background:There is now intense interest in the role of HIV-specific antibodies and the engagement of FcγR functions in the control and prevention of HIV infection. The analyses of the RV144 vaccine trial, natural progression cohorts, and macaque models all point to a role for Fc-dependent effector functions, such as cytotoxicity (ADCC) or phagocytosis (ADCP), in the control of HIV. However, reliable assays that can be reproducibly used across different laboratories to measure Fcdependent functions, such as antibody dependent cellular cytotoxicity (ADCC) are limited. Method: This brief review highlights the importance of Fc properties for immunity to HIV, particularly via FcγR diversity and function. We discuss assays used to study FcR mediated functions of HIV-specific Ab, including our recently developed novel cell-free ELISA using homo-dimeric FcγR ectodomains to detect functionally relevant viral antigen-specific antibodies. Results: The binding of these dimeric FcγR ectodomains, to closely spaced pairs of IgG Fc, mimics the engagement and cross-linking of Fc receptors by IgG opsonized virions or infected cells as the essential prerequisite to the induction of Ab-dependent effector functions. The dimeric FcγR ELISA reliably correlates with ADCC in patient responses to influenza. The assay is amenable to high throughput and could be standardized across laboratories. Conclusion: We propose the assay has broader implications for the evaluation of the quality of antibody responses in viral infections and for the rapid evaluation of responses in vaccine development campaigns for HIV and other viral infections.

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IgG Fc Receptor III Homologues in Nonhuman Primate Species: Genetic Characterization and Ligand Interactions

Cited by 88 publications

References 59 publications

Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host

Effect of B-Cell Depletion on Viral Replication and Clinical Outcome of Simian Immunodeficiency Virus Infection in a Natural Host

Nonhuman Primate IgA: Genetic Heterogeneity and Interactions with CD89

Antibody functional assays as measures of Fc receptor-mediated immunity to HIV - new technologies and their impact on the HIV vaccine field.

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