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PMID: 15630142 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

An antagonist peptide mediates positive selection and CD4 lineage commitment of MHC class II-restricted T cells in the absence of CD4.

The Journal of experimental medicine ·Vol. 201 ·No. 1 ·2005-01-03 ·Pages 149-58

Kao H, Allen PM

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.

MeSH Terms
Amino Acid Sequence Animals Bone Marrow Cells/immunology,radiation effects CD4 Antigens/genetics,immunology CD4-Positive T-Lymphocytes/cytology,immunology,metabolism Cell Lineage/immunology Cell Proliferation DNA Primers Flow Cytometry Histocompatibility Antigens Class II/immunology Interleukin-2/metabolism Ligands Mice Mice, Transgenic Molecular Sequence Data Peptides/genetics,immunology,metabolism Receptors, Antigen, T-Cell/immunology,metabolism Reverse Transcriptase Polymerase Chain Reaction Selection, Genetic
Chemicals
CD4 Antigens DNA Primers Histocompatibility Antigens Class II Interleukin-2 Ligands Peptides Receptors, Antigen, T-Cell
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kao Henry
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Allen Paul M
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20041574
Published
2005-01-03
Pages
149-58
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212763
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20041574 PMC Full Text View journal details
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