Evidence map›Paper›PMID 10790426›Full record

ArticleThe Journal of experimental medicine2000

Cytoplasmic processing is a prerequisite for presentation of an endogenous antigen by major histocompatibility complex class II proteins.

J D Lich, J F Elliott, J S Blum

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

55 citing papers in PubMed, 147 citations in OpenAlex.

  1. Article
  2. Multi-antigen spherical nucleic acid cancer vaccines.Nature biomedical engineering · 2023
    Article
  3. Article
  4. The role of autophagy in viral infections.Journal of biomedical science · 2023
    Review
  5. Article
  6. Peptide Modification Diminishes HLA Class II-restricted CD4International journal of molecular sciences · 2022
    Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Immunogenetics of Disease-Causing Inflammation in Sarcoidosis.Clinical reviews in allergy & immunology · 2015
    Review
  18. Article
  19. Article
  20. 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

3 authors at 2 institutions in 2 countries.

J D LichDepartment of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
J F Elliott
J S Blum
Indiana University – Purdue University Indianapolis · USUniversity of Alberta · CA

Funding

REGULATION OF HEMATOPOIETIC CELL PRODUCTIONT32DK007519 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI KAPLAN, MARK H · 1986 to 2020
$7.1M
MHC Class II-restricted Cytoplasmic Antigen PresentationR01AI049589 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI BLUM, JANICE S · 2001 to 2005
$1.7M
MHC Class II-restricted Cytoplasmic Antigen PresentationR56AI049589 · NIAID · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI BLUM, JANICE S · 2007 to 2007
$300k
NIAID NIH HHS R01 AI049589NIAID NIH HHS R56 AI049589NIDDK NIH HHS T32 DK007519NIDDK NIH HHS T32DK07519
6 · The paper itself

Abstract

Biochemical and functional studies have demonstrated major histocompatibility complex (MHC) class II-restricted presentation of select epitopes derived from cytoplasmic antigens, with few insights into the processing reactions necessary for this alternate pathway. Efficient presentation of an immunodominant epitope derived from glutamate decarboxylase (GAD) was observed regardless of whether this antigen was delivered exogenously or via a cytoplasmic route into human histocompatibility leukocyte antigen class II-DR4(+) antigen-presenting cells. Presentation of exogenous as well as cytoplasmic GAD required the intersection of GAD peptides and newly synthesized class II proteins. By contrast, proteolytic processing of this antigen was highly dependent upon the route of antigen delivery. Exogenous GAD followed the classical pathway for antigen processing, with an absolute requirement for endosomal/lysosomal acidification as well as cysteine and aspartyl proteases resident within these organelles. Presentation of endogenous GAD was dependent upon the action of cytoplasmic proteases, including the proteasome and calpain. Thus, translocation of processed antigen from the cytoplasm into membrane organelles is necessary for class II-restricted presentation via this alternate pathway. Further trimming of these peptides after translocation was mediated by acidic proteases within endosomes/lysosomes, possibly after or before class II antigen binding. These studies suggest that processing of exogenous and cytoplasmic proteins occurs through divergent but overlapping pathways. Furthermore, two cytoplasmic proteases, the proteasome and calpain, appear to play important roles in MHC class II-restricted antigen presentation.

Indexed as

Antigen PresentationProtein Processing, Post-TranslationalAspartic Acid EndopeptidasesAutoantigensBiological TransportCell PolarityCysteine EndopeptidasesCytoplasmEndocytosisEndosomesGlutamate DecarboxylaseHistocompatibility Antigens Class IIHLA-DR4 AntigenImmunodominant EpitopesLysosomesPeptide FragmentsAspartic Acid EndopeptidasesAutoantigensCysteine EndopeptidasesGlutamate DecarboxylaseHistocompatibility Antigens Class IIHLA-DR4 AntigenImmunodominant EpitopesPeptide Fragments

Identifiers

PMID10790426
PMCPMC2213437
OpenAlexW2125397071

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.