Evidence map›Paper›PMID 24853397›Full record

ArticleMolecular immunology2014

γδ T cells recognize the insulin B:9-23 peptide antigen when it is dimerized through thiol oxidation.

M Kemal Aydintug, Li Zhang, Chao Wang, Dongchun Liang, J M Wands, Aaron W Michels, Brooke Hirsch, Brian J Day, Gongyi Zhang, Deming Sun and 3 more

Open access · greenAbstract read
In one paragraph

Article in Molecular immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. A Special Connection between γδ T Cells and Natural Antibodies?Archivum immunologiae et therapiae experimentalis · 2016
    Review
  11. Review
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 4 institutions in 1 country.

M Kemal AydintugIntegrated Department of Immunology, National Jewish Health and University of Colorado Denver, 1400 Jackson Street, Denver, CO 80206, USA.
Li ZhangBarbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.
Chao WangIntegrated Department of Immunology, National Jewish Health and University of Colorado Denver, 1400 Jackson Street, Denver, CO 80206, USA.
Dongchun LiangDepartment of Ophthalmology, Doheny Eye Institute, University of Southern California, Los Angeles, CA 90033, USA.
J M WandsIntegrated Department of Immunology, National Jewish Health and University of Colorado Denver, 1400 Jackson Street, Denver, CO 80206, USA.
Aaron W MichelsBarbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.
Brooke HirschDepartment of Biomolecular Structure, University of Colorado Denver, Anschutz Medical Campus, Aurora CO 80045, USA.
Brian J DayDepartment of Medicine, National Jewish Health, 1400 Jackson Street, CO 80206, USA.
Gongyi ZhangIntegrated Department of Immunology, National Jewish Health and University of Colorado Denver, 1400 Jackson Street, Denver, CO 80206, USA.
Deming SunDepartment of Ophthalmology, Doheny Eye Institute, University of Southern California, Los Angeles, CA 90033, USA.
George S EisenbarthBarbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO 80045, USA.
Rebecca L O'BrienIntegrated Department of Immunology, National Jewish Health and University of Colorado Denver, 1400 Jackson Street, Denver, CO 80206, USA.
Willi K BornIntegrated Department of Immunology, National Jewish Health and University of Colorado Denver, 1400 Jackson Street, Denver, CO 80206, USA. Electronic address: bornw@njhealth.org.
National Jewish Health · USUniversity of Colorado Denver · USUniversity of Southern California · USUniversity of Colorado Anschutz Medical Campus · US

Funding

UCHSC DIABETES ENDOCRINOLOGY RESEARCH CENTERP30DK057516 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI HUTTON, JOHN C · 2000 to 2010
$14.0M
IN VIVO NOD EVALUATION OF A PATHOGENIC INSULIN PEPTIDER01DK055969 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI EISENBARTH, GEORGE S · 1998 to 2009
$2.2M
Regulation by Gammadelta T Cells of Autoimmune Uveitis (EAU)R01EY022403 · NEI · DOHENY EYE INSTITUTE · PI SUN, DEMING · 2012 to 2015
$1.6M
The role of gamma/delta T cells in type 1 diabetesR21AI097962 · NIAID · NATIONAL JEWISH HEALTH · PI O'BRIEN, REBECCA L. · 2012 to 2013
$436k
NEI NIH HHS R01 EY022403NIAID NIH HHS R21 AI097962NIAID NIH HHS R21AI097962NIDDK NIH HHS P30 DK057516NIDDK NIH HHS P30 DK57516NIDDK NIH HHS R01 DK055969NIDDK NIH HHS R01DK55969PHS HHS 2U19A1050864
6 · The paper itself

Abstract

The insulin peptide B:9-23 is a natural antigen in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). In addition to αβ T cells and B cells, γδ T cells recognize the peptide and infiltrate the pancreatic islets where the peptide is produced within β cells. The peptide contains a cysteine in position 19 (Cys19), which is required for the γδ but not the αβ T cell response, and a tyrosine in position 16 (Tyr16), which is required for both. A peptide-specific mAb, tested along with the T cells, required neither of the two amino acids to bind the B:9-23 peptide. We found that γδ T cells require Cys19 because they recognize the peptide antigen in an oxidized state, in which the Cys19 thiols of two peptide molecules form a disulfide bond, creating a soluble homo-dimer. In contrast, αβ T cells recognize the peptide antigen as a reduced monomer, in complex with the MHCII molecule I-A(g7). Unlike the unstructured monomeric B:9-23 peptide, the γδ-stimulatory homo-dimer adopts a distinct secondary structure in solution, which differs from the secondary structure of the corresponding portion of the native insulin molecule. Tyr16 is required for this adopted structure of the dimerized insulin peptide as well as for the γδ response to it. This observation is consistent with the notion that γδ T cell recognition depends on the secondary structure of the dimerized insulin B:9-23 antigen.

Indexed as

AnimalsAntigensDiabetes Mellitus, Type 1DimerizationFemaleInsulinMiceMice, Inbred NODOxidation-ReductionPeptide FragmentsReceptors, Antigen, T-Cell, gamma-deltaSulfhydryl CompoundsAntigensInsulininsulin B (9-23)Peptide FragmentsReceptors, Antigen, T-Cell, gamma-deltaSulfhydryl CompoundsAutoimmune diabetesAutoreactivityGamma delta T cellsInsulinOxidationT Cell Receptor

Identifiers

PMID24853397
PMCPMC4091716
OpenAlexW1971639083

What OpenQuestion holds

Textmetadata
LicenceTDM
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.