Evidence map›Paper›PMID 25263124›Full record

ArticleNature immunology2014

N-glycosylation bidirectionally extends the boundaries of thymocyte positive selection by decoupling Lck from Ca²⁺ signaling.

Raymond W Zhou, Haik Mkhikian, Ani Grigorian, Amanda Hong, David Chen, Araz Arakelyan, Michael Demetriou

Abstract read
PubMed Publisher
In one paragraph

Article in Nature immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.1field-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

37 citing papers in PubMed, 61 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
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  6. Review
  7. Immunometabolism (Cobham, Surrey) · 2023
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. The Role of B Cell and T Cell Glycosylation in Systemic Lupus Erythematosus.International journal of molecular sciences · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Metabolic regulation of T cell development.Frontiers in immunology · 2022
    Review
  17. Review
  18. The Role of Glycosylation in Inflammatory Diseases.Advances in experimental medicine and biology · 2021
    Article
  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

7 authors at 1 institution in 1 country.

Raymond W Zhou1] Department of Neurology, University of California, Irvine, Irvine, California, USA. [2] Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA. [3] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
Haik Mkhikian1] Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA. [2] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
Ani Grigorian1] Department of Neurology, University of California, Irvine, Irvine, California, USA. [2] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
Amanda HongDepartment of Neurology, University of California, Irvine, Irvine, California, USA.
David ChenDepartment of Neurology, University of California, Irvine, Irvine, California, USA.
Araz ArakelyanDepartment of Neurology, University of California, Irvine, Irvine, California, USA.
Michael Demetriou1] Department of Neurology, University of California, Irvine, Irvine, California, USA. [2] Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, California, USA. [3] Institute for Immunology, University of California, Irvine, Irvine, California, USA.
University of California, Irvine · US

Funding

T cell regulation by N-glycosylationR01AI053331 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI DEMETRIOU, MICHAEL · 2003 to 2014
$3.5M
N-glycosylation as a downstream effector of Interleukin-7F30HL108451 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI MKHIKIAN, HAIK · 2011 to 2015
$202k
NHLBI NIH HHS F30HL108451NIAID NIH HHS R01AI053331
6 · The paper itself

Abstract

Positive selection of diverse yet self-tolerant thymocytes is vital to immunity and requires a limited degree of T cell antigen receptor (TCR) signaling in response to self peptide-major histocompatibility complexes (self peptide-MHCs). Affinity of newly generated TCR for peptide-MHC primarily sets the boundaries for positive selection. We report that N-glycan branching of TCR and the CD4 and CD8 coreceptors separately altered the upper and lower affinity boundaries from which interactions between peptide-MHC and TCR positively select T cells. During thymocyte development, N-glycan branching varied approximately 15-fold. N-glycan branching was required for positive selection and decoupled Lck signaling from TCR-driven Ca(2+) flux to simultaneously promote low-affinity peptide-MHC responses while inhibiting high-affinity ones. Therefore, N-glycan branching imposes a sliding scale on interactions between peptide-MHC and TCR that bidirectionally expands the affinity range for positive selection.

Indexed as

AcyltransferasesAnimalsCalciumCalcium SignalingCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCells, CulturedGlycosylationLymphocyte ActivationLymphocyte Specific Protein Tyrosine Kinase p56(lck)Major Histocompatibility ComplexMiceMice, Inbred C57BLMice, KnockoutN-AcetylglucosaminyltransferasesAcyltransferasesalpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferasealpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferaseCalciumLymphocyte Specific Protein Tyrosine Kinase p56(lck)MGAT1 protein, mouseN-AcetylglucosaminyltransferasesPolysaccharidesReceptors, Antigen, T-Cell

Identifiers

PMID25263124
OpenAlexW2045741926

What OpenQuestion holds

Textmetadata
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.