Evidence map›Paper›PMID 41445744›Full record

ArticleFrontiers in immunology2025

Cross-species analysis of FcγRIIa/b (CD32a/b) polymorphisms at position 131: structural and functional insights into the mechanism of IgG- mediated phagocytosis in human and macaque.

William D Tolbert, Paula B Nhan, Haleigh E Conley, Xiaoxuan Ge, Monika Chandravanshi, Madeleine Lee, Julianna Veilleux, Marek Korzeniowski, Suneetha Gottumukkala, Margaret E Ackerman and 2 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

William D TolbertInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Paula B NhanInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Haleigh E ConleyDepartment of Surgery, Duke University School of Medicine, Durham, NC, United States.
Xiaoxuan GeThayer School of Engineering, Dartmouth College, Hanover, NH, United States.
Monika ChandravanshiInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Madeleine LeeInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Julianna VeilleuxInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Marek KorzeniowskiInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Suneetha GottumukkalaInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
Margaret E AckermanThayer School of Engineering, Dartmouth College, Hanover, NH, United States.
Justin PollaraDepartment of Surgery, Duke University School of Medicine, Durham, NC, United States.
Marzena PazgierInfectious Disease Division, Department of Medicine of the Uniformed Services University of the Health Sciences, Bethesda, MD, United States.

Funding

Structure-Function Analytics CoreP01AI162242 · NIAID · DUKE UNIVERSITY · PI TOMARAS, GEORGIA DORIS · 2021 to 2025
$22.2M
Ruth L. Kirschstein National Research Service Award (NRSA)- T32T32AI007392 · NIAID · DUKE UNIVERSITY · PI Amy Lynn Corneli, Guido Ferrari · 1990 to 2026
$9.8M
Targeting the HIV-1 reservoir at cART initiation with CD4-mimetic interventionsR01AI186809 · NIAID · YALE UNIVERSITY · PI Priti Kumar, JOSEPH G SODROSKI · 2024 to 2026
$4.0M
Tracking the evolutionary trajectory of neutralizing antibodies following BG505 SOSIP immunizationR01AI174979 · NIAID · UNIVERSITY OF WASHINGTON · PI DERDEYN, CYNTHIA ANN · 2023 to 2025
$3.9M
A new strategy to eliminate HIV-1-infected cells by unlocking the Env trimerR01AI174908 · NIAID · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI Marzena Elzbieta Pazgier · 2023 to 2026
$2.8M
Molecular characterization and modeling efficient antibody effector functionR01AI186995 · NIAID · DARTMOUTH COLLEGE · PI Margaret E Ackerman · 2025 to 2026
$884k
IgG and FcR Characterization in Small Animal Models of RespiratoryDiseaseR21AI176640 · NIAID · DARTMOUTH COLLEGE · PI ACKERMAN, MARGARET E · 2023 to 2024
$445k
NIAID NIH HHS P01 AI162242NIAID NIH HHS R01 AI174908NIAID NIH HHS R01 AI174979NIAID NIH HHS R01 AI186809NIAID NIH HHS R01 AI186995NIAID NIH HHS R21 AI176640NIAID NIH HHS T32 AI007392
6 · The paper itself

Abstract

Introduction: Antibodies play a critical role in immunity in part by mediating clearance of pathogens and infected cells by antibody-dependent cellular phagocytosis (ADCP) through engagement of Fc gamma receptors (FcγRs) on innate immune cells. Among these, FcγRIIa (CD32a) is a key activating receptor expressed on macrophages, dendritic cells, and other antigen-presenting cells. Its affinity for IgG and ability to mediate ADCP is influenced by allelic polymorphisms. In humans, a single amino acid polymorphism at position 131, where histidine (H) is substituted with arginine (R), leads to decreased IgG1 and IgG2 subclass binding affinity and, consequently, lower efficiency of phagocytic responses. Rhesus macaques ( Methods: We determined the structures of complexes formed by each variant with IgG1 Fc and those formed by the higher affinity variant with IgG2 Fc for both species by x-ray crystallography and linked these structures to affinity and activity using SPR and an ADCP assay. We also determined the structure of human inhibitory FcγRIIb (CD32b) in complex with IgG1 Fc by x-ray crystallography. Results: Through analysis of these structures, our studies reveal that FcγRIIa engagement is minimally influenced by Fc glycan composition, distinguishing it from FcγRIIIa whose affinity is strongly influenced by glycan-composition. Comparative structures of human and macaque FcγRIIa variants demonstrate species- and allele-specific differences in Fc binding, but our functional assays showed only minimal allele-specific effects in humans. In contrast, allele-specific effects in macaques were highly significant; the macaque P Conclusion: These insights highlight fundamental interspecies and allelic distinctions that are critical for interpreting FcγRIIa-mediated effector functions in macaque models and for optimizing translational antibody and vaccine design.

Indexed as

Immunoglobulin GPhagocytosisPolymorphism, GeneticReceptors, IgGAnimalsHumansMacaca mulattaSpecies SpecificityFc gamma receptor IIAImmunoglobulin GReceptors, IgGCD32Fc-effector functionFcγRIIa His/Arg131FcγRIIa His/Pro131human Homo sapiensIgG1(Fc)-FcγRII complex structureIgG2(Fc)-FcγRIIa complex structurerhesus macaque Macaca mulatta

Identifiers

PMID41445744
PMCPMC12723028

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.