Evidence map›Paper›PMID 39392756›Full record

ArticleCell reports2024

Human antibody polyreactivity is governed primarily by the heavy-chain complementarity-determining regions.

Hsin-Ting Chen, Yulei Zhang, Jie Huang, Manali Sawant, Matthew D Smith, Nandhini Rajagopal, Alec A Desai, Emily Makowski, Giuseppe Licari, Yunxuan Xie and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

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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

13 authors.

Hsin-Ting ChenDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Yulei ZhangDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Jie HuangDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Manali SawantDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Matthew D SmithDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Nandhini RajagopalBiotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
Alec A DesaiDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Emily MakowskiDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Giuseppe LicariBiotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
Yunxuan XieDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Michael S MarlowBiotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
Sandeep KumarBiotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
Peter M TessierDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ptessier@umich.edu.

Funding

CD98hc Brain Shuttles for Delivering Off-the-shelf Neuroprotective Antibodies in Alzheimer's DiseaseR01AG080016 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Colin Fred Greineder, Peter M Tessier · 2023 to 2026
$3.2M
Design and Evolution of Polyvalent Domain Antibodies Specific for Tau AggregatesRF1AG059723 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KANE, RAVI S., TESSIER, PETER M · 2018 to 2022
$2.4M
Structure-guided antibody targeting of pre-selected epitopes in amyloidogenic aggregatesR35GM136300 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESSIER, PETER M · 2020 to 2024
$1.5M
Mutational Analysis of Tradeoffs between Receptor Affinity and Antibody Escape for SARS-CoV-2 Variants of ConcernR21AI171844 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TESSIER, PETER M · 2022 to 2023
$405k
NIAID NIH HHS R21 AI171844NIA NIH HHS R01 AG080016NIA NIH HHS RF1 AG059723NIGMS NIH HHS R35 GM136300
6 · The paper itself

Abstract

Although antibody variable regions mediate antigen-specific binding, they can also mediate non-specific interactions with non-cognate antigens, impacting diverse immunological processes and the efficacy, safety, and half-life of antibody therapeutics. To understand the molecular basis of antibody non-specificity, we sorted two dissimilar human naïve antibody libraries against multiple reagents to enrich for variants with different levels of polyreactivity. Sequence analysis of >300,000 paired antibody variable regions revealed that the heavy chain primarily mediates human antibody polyreactivity, and this is due to the high positive charge, high hydrophobicity, and combinations thereof in the corresponding complementarity-determining regions, which can be predicted using a machine learning model developed in this work. Notably, a subset of the most important features governing antibody non-specific interactions, namely those that contain tyrosine, also govern specific antigen recognition. Our findings are broadly relevant for understanding fundamental aspects of antibody molecular recognition and the applied aspects of antibody-drug design.

Indexed as

Complementarity Determining RegionsImmunoglobulin Heavy ChainsAmino Acid SequenceAntibodiesAntibody SpecificityHumansAntibodiesComplementarity Determining RegionsImmunoglobulin Heavy Chainsantibody engineeringCP: Immunologydeep sequencingdevelopabilitymachine learningnon-specific bindingnonspecificityoff-target bindingpharmacokineticpolyspecificityrepertoire

Identifiers

PMID39392756
PMCPMC11564698

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Registered trials

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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.