Evidence map›Paper›PMID 35867757›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Genetic and structural basis of the human anti-α-galactosyl antibody response.

David B Langley, Peter Schofield, Damien Nevoltris, Jennifer Jackson, Katherine J L Jackson, Tim J Peters, Melanie Burk, Jacqueline M Matthews, Antony Basten, Christopher C Goodnow and 3 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
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

14 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Is Zebrafish a Good Model for the Alpha-Gal Syndrome?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Genetic and structural basis of the human anti-α-galactosyl antibody response.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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 at 2 institutions in 1 country.

David B LangleyGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0003-2752-0041
Peter SchofieldGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0002-8046-3667
Damien NevoltrisGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0002-0981-5703
Jennifer JacksonGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0003-4237-5233
Katherine J L JacksonGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
Tim J PetersGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
Melanie BurkTick-induced Allergies Research and Awareness Centre, Sydney, NSW 2065, Australia.
Jacqueline M MatthewsSchool of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
Antony BastenGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0003-2200-7695
Christopher C GoodnowGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0001-5296-6155
Sheryl van NunenTick-induced Allergies Research and Awareness Centre, Sydney, NSW 2065, Australia.
Joanne H ReedGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0002-7585-7848
Daniel ChristGarvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.ORCID 0000-0002-7313-3977
Garvan Institute of Medical Research · AUThe University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Humans lack the capacity to produce the Galα1-3Galβ1-4GlcNAc (α-gal) glycan, and produce anti-α-gal antibodies upon exposure to the carbohydrate on a diverse set of immunogens, including commensal gut bacteria, malaria parasites, cetuximab, and tick proteins. Here we use X-ray crystallographic analysis of antibodies from α-gal knockout mice and humans in complex with the glycan to reveal a common binding motif, centered on a germline-encoded tryptophan residue at Kabat position 33 (W33) of the complementarity-determining region of the variable heavy chain (CDRH1). Immunoglobulin sequencing of anti-α-gal B cells in healthy humans and tick-induced mammalian meat anaphylaxis patients revealed preferential use of heavy chain germline IGHV3-7, encoding W33, among an otherwise highly polyclonal antibody response. Antigen binding was critically dependent on the presence of the germline-encoded W33 residue for all of the analyzed antibodies; moreover, introduction of the W33 motif into naive IGHV3-23 antibody phage libraries enabled the rapid selection of α-gal binders. Our results outline structural and genetic factors that shape the human anti-α-galactosyl antibody response, and provide a framework for future therapeutics development.

Indexed as

AnaphylaxisAntibodiesFood HypersensitivityImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionTick-Borne DiseasesTrisaccharidesAnimalsAntibody FormationAntigen-Antibody ComplexCrystallography, X-RayHumansMiceMice, KnockoutPeptide LibraryProtein Conformationalpha-galactosyl epitopeAntibodiesAntigen-Antibody ComplexImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionPeptide LibraryTrisaccharidesalpha-galactoseantibodygermline restrictionmammalian meat allergy

Identifiers

PMID35867757
PMCPMC9282431
OpenAlexW4284882429

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.