Positive Selection of Cd4+ T Cells Is Induced in Vivo by Agonist and Inhibited by Antagonist Peptides

Hdl Handle:
http://hdl.handle.net/10675.2/554
Title:
Positive Selection of Cd4+ T Cells Is Induced in Vivo by Agonist and Inhibited by Antagonist Peptides
Authors:
Kraj, Piotr; Pacholczyk, Rafal; Ignatowicz, Hanna; Kisielow, Pawel; Jensen, Peter; Ignatowicz, Leszek
Abstract:
The nature of peptides that positively select T cells in the thymus remains poorly defined. Here we report an in vivo model to study the mechanisms of positive selection of CD4+ T cells. We have restored positive selection of TCR transgenic CD4+ thymocytes, arrested at the CD4+CD8+ stage, due to the lack of the endogenously selecting peptide(s), in mice deficient for H2-M and invariant chain. A single injection of soluble agonist peptide(s) initiated positive selection of CD4+ transgenic T cells that lasted for up to 14 days. Positively selected CD4+ T cells repopulated peripheral lymphoid organs and could respond to the antigenic peptide. Furthermore, coinjection of the antagonist peptide significantly inhibited agonist-driven positive selection. Hence, contrary to the prevailing view, positive selection of CD4+ thymocytes can be induced in vivo by agonist peptides and may be a result of accumulation of signals from TCR engaged by different peptides bound to major histocompatibility complex class II molecules. We have also identified a candidate natural agonist peptide that induces positive selection of CD4+ TCR transgenic thymocytes.
Citation:
J Exp Med. 2001 Aug 20; 194(4):407-416
Issue Date:
20-Aug-2001
URI:
http://hdl.handle.net/10675.2/554
PubMed ID:
11514598
PubMed Central ID:
PMC2193504
Type:
Article
ISSN:
1540-9538
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorKraj, Piotren_US
dc.contributor.authorPacholczyk, Rafalen_US
dc.contributor.authorIgnatowicz, Hannaen_US
dc.contributor.authorKisielow, Pawelen_US
dc.contributor.authorJensen, Peteren_US
dc.contributor.authorIgnatowicz, Leszeken_US
dc.date.accessioned2012-10-26T16:26:39Z-
dc.date.available2012-10-26T16:26:39Z-
dc.date.issued2001-08-20en_US
dc.identifier.citationJ Exp Med. 2001 Aug 20; 194(4):407-416en_US
dc.identifier.issn1540-9538en_US
dc.identifier.pmid11514598en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/554-
dc.description.abstractThe nature of peptides that positively select T cells in the thymus remains poorly defined. Here we report an in vivo model to study the mechanisms of positive selection of CD4+ T cells. We have restored positive selection of TCR transgenic CD4+ thymocytes, arrested at the CD4+CD8+ stage, due to the lack of the endogenously selecting peptide(s), in mice deficient for H2-M and invariant chain. A single injection of soluble agonist peptide(s) initiated positive selection of CD4+ transgenic T cells that lasted for up to 14 days. Positively selected CD4+ T cells repopulated peripheral lymphoid organs and could respond to the antigenic peptide. Furthermore, coinjection of the antagonist peptide significantly inhibited agonist-driven positive selection. Hence, contrary to the prevailing view, positive selection of CD4+ thymocytes can be induced in vivo by agonist peptides and may be a result of accumulation of signals from TCR engaged by different peptides bound to major histocompatibility complex class II molecules. We have also identified a candidate natural agonist peptide that induces positive selection of CD4+ TCR transgenic thymocytes.en_US
dc.rights© 2001 The Rockefeller University Pressen_US
dc.subjectOriginal Articleen_US
dc.titlePositive Selection of Cd4+ T Cells Is Induced in Vivo by Agonist and Inhibited by Antagonist Peptidesen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2193504en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-

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