Evidence map›Paper›PMID 21850230›Full record

ArticlePloS one2011

High-throughput identification of potential minor histocompatibility antigens by MHC tetramer-based screening: feasibility and limitations.

Pleun Hombrink, Sine R Hadrup, Arne Bakker, Michel G D Kester, J H Frederik Falkenburg, Peter A von dem Borne, Ton N M Schumacher, Mirjam H M Heemskerk

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 32 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Frontiers in immunology · 2018
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Broadening the repertoire of melanoma-associated T-cell epitopes.Cancer immunology, immunotherapy : CII · 2015
    Article
  13. Article
  14. T-cell responses to oncogenic merkel cell polyomavirus proteins distinguish patients with merkel cell carcinoma from healthy donors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014
    Article
  15. Article
  16. Article
  17. The human leukocyte antigen-presented ligandome of B lymphocytes.Molecular & cellular proteomics : MCP · 2013
    Article
  18. Review
  19. Article
  20. 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

8 authors at 3 institutions in 1 country.

Pleun HombrinkDepartment of Hematology, Leiden University Medical Center, Leiden, The Netherlands. p.hombrink@lumc.nl
Sine R Hadrup
Arne Bakker
Michel G D Kester
J H Frederik Falkenburg
Peter A von dem Borne
Ton N M Schumacher
Mirjam H M Heemskerk
Leiden University Medical Center · NLOncode Institute · NLThe Netherlands Cancer Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

T-cell recognition of minor histocompatibility antigens (MiHA) plays an important role in the graft-versus-tumor (GVT) effect of allogeneic stem cell transplantation (allo-SCT). However, the number of MiHA identified to date remains limited, making clinical application of MiHA reactive T-cell infusion difficult. This study represents the first attempt of genome-wide prediction of MiHA, coupled to the isolation of T-cell populations that react with these antigens. In this unbiased high-throughput MiHA screen, both the possibilities and pitfalls of this approach were investigated. First, 973 polymorphic peptides expressed by hematopoietic stem cells were predicted and screened for HLA-A2 binding. Subsequently a set of 333 high affinity HLA-A2 ligands was identified and post transplantation samples from allo-SCT patients were screened for T-cell reactivity by a combination of pMHC-tetramer-based enrichment and multi-color flow cytometry. Using this approach, 71 peptide-reactive T-cell populations were generated. The isolation of a T-cell line specifically recognizing target cells expressing the MAP4K1(IMA) antigen demonstrates that identification of MiHA through this approach is in principle feasible. However, with the exception of the known MiHA HMHA1, none of the other T-cell populations that were generated demonstrated recognition of endogenously MiHA expressing target cells, even though recognition of peptide-loaded targets was often apparent. Collectively these results demonstrate the technical feasibility of high-throughput analysis of antigen-specific T-cell responses in small patient samples. However, the high-sensitivity of this approach requires the use of potential epitope sets that are not solely based on MHC binding, to prevent the frequent detection of T-cell responses that lack biological relevance.

Indexed as

Cell LineEpitopesFlow CytometryGene Expression ProfilingHLA-A2 AntigenHumansMajor Histocompatibility ComplexMinor Histocompatibility AntigensOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideT-LymphocytesEpitopesHLA-A2 AntigenMinor Histocompatibility Antigens

Identifiers

PMID21850230
PMCPMC3151248
OpenAlexW2003445572

What OpenQuestion holds

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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.