Evidence map›Paper›PMID 20220067›Full record

ArticleHaematologica2010

The nature of peptides presented by an HLA class I low expression allele.

Jan Hinrichs, Daniel Föll, Christina Bade-Döding, Trevor Huyton, Rainer Blasczyk, Britta Eiz-Vesper

Abstract read
In one paragraph

Article in Haematologica, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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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

4 citing papers in PubMed.

  1. Article
  2. Divergent Peptide Presentations of HLA-AFrontiers in immunology · 2019
    Article
  3. Article
  4. Article
4 · The record

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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

6 authors.

Jan HinrichsInstitute for Transfusion Medicine, Hannover Medical School, Hannover, Germany.
Daniel Föll
Christina Bade-Döding
Trevor Huyton
Rainer Blasczyk
Britta Eiz-Vesper

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe functional integrity of human leukocyte antigen low expression variants is a prerequisite for considering them as essential in the matching process of hematopoietic stem cell donors and recipients to diminish the risk of serious complications such as graft-versus-host disease or graft rejection. The HLA-A*3014L variant has a disulfide bridge missing in the alpha2 domain which could affect peptide binding and presentation to T cells. DESIGN AND

methodsHLA-A*3014L and HLA-A*3001 were expressed as truncated variants and peptides were eluted and subjected to pool sequencing by Edman degradation as well as to single-peptide sequencing by mass spectrometry. Quantitative analysis of binding peptides presented in vivo was performed by a flow cytometric peptide-binding assay using HLA-A*3001 and HLA-A*3014L-expressing B-LCLs.

resultsThe truncated HLA-A*3014L protein was secreted in the supernatant and it was possible to elute and sequence peptides. Sequence analysis of these eluted peptides revealed no relevant differences to the peptide motif of HLA-A*3001, indicating that the Cys164Ser substitution does not substantially alter the spectrum of presented peptides. Strong binding of one of the shared in vivo identified HLA-A*3001/3014L ligands was confirmed in the peptide-binding assay.

conclusionsThis study is the first to demonstrate that HLA low expression variants are able to present peptides and, thus, can be considered as functionally active. When comparing peptide motifs, it is likely that HLA-A*3014L and HLA-A*3001 represent a permissive mismatch with low allogenicity in hematopoietic stem cell transplantation. These results indicate that surface expression, as well as peptide-binding data of HLA variants with similar disulfide bridge variations (e.g. HLA-A*3211Q) need to be considered as functionally active in an allogeneic hematopoietic stem cell transplantation setting as long as the opposite has not been shown. Otherwise a relevant but not considered HLA mismatch could result in a severe allogeneic T-cell response and graft-versus-host disease.

Indexed as

AllelesAmino Acid MotifsAmino Acid SequenceAmino Acid SubstitutionBinding SitesGene ExpressionHEK293 CellsHLA-A AntigensHumansMass SpectrometryModels, MolecularMutagenesisPeptidesProtein BindingProtein Structure, TertiarySequence Analysis, ProteinHLA-A*30:01 antigenHLA-A AntigensPeptides

Identifiers

PMID20220067
PMCPMC2913087

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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.