ArticleThe Journal of experimental medicine2005
An antagonist peptide mediates positive selection and CD4 lineage commitment of MHC class II-restricted T cells in the absence of CD4.
Article in The Journal of experimental medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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Who cites it
8 citing papers in PubMed.
- Cooperative binding of T cell receptor and CD4 to peptide-MHC enhances antigen sensitivity.Nature communications · 2022Article
- Complete Multilineage CD4 Expression Defect Associated With Warts Due to an Inherited Homozygous CD4 Gene Mutation.Frontiers in immunology · 2019Article
- Reciprocal TCR-CD3 and CD4 Engagement of a Nucleating pMHCII Stabilizes a Functional Receptor Macrocomplex.Cell reports · 2018Article
- Force-Regulated In Situ TCR-Peptide-Bound MHC Class II Kinetics Determine Functions of CD4+ T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- The TCR repertoires of regulatory and conventional T cells specific for the same foreign antigen are distinct.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- microRNAs at the regulatory frontier: an investigation into how microRNAs impact the development and effector functions of CD4 T cells.Immunologic research · 2011Article
- Regulated movement of CD4 in and out of the immunological synapse.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
- Protein kinase C-theta is required for efficient positive selection.Journal of immunology (Baltimore, Md. : 1950) · 2008Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CD4 coreceptor works together with the T cell receptor (TCR) to deliver signals to the developing thymocyte, yet its specific contribution to positive selection and CD4 lineage commitment remains unclear. To resolve this, we used N3.L2 TCR transgenic, RAG-, and CD4-deficient mice, which are severely impaired in positive selection, and asked whether altered peptide ligands can replace CD4 function in vivo. Remarkably, in the presence of antagonist ligands that normally deleted CD4+ T cells in wild-type mice, we induced positive selection of functional CD4 lineage T cells in mice deficient in CD4. We show that the kinetic threshold for positive and negative selection was lowered in the absence of CD4, with no evident skewing toward the CD8 lineage with weaker ligands. These results suggest that CD4 is dispensable as long as the affinity threshold for positive selection is sustained, and strongly argue that CD4 does not deliver a unique instructional signal for lineage commitment.
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Registered trials
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.