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Nat Immunol. 2009 Nov;10(11):1155-61. doi: 10.1038/ni.1796. Epub 2009 Oct 4.

An endogenous peptide positively selects and augments the activation and survival of peripheral CD4+ T cells.

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Department of Immunology and Pathology, Washington University School of Medicine, St. Louis, Missouri, USA.


Although CD4(+) and CD8(+) T cells differ in the strength of their positively selecting signal, endogenous positively selecting ligands have been identified only for major histocompatibility complex (MHC) class I-restricted T cell antigen receptors (TCRs). Here we screened for ligands able to positively select MHC class II-restricted TCRs using thymocytes from four I-E(k)-restricted TCR-transgenic mice and a large panel of self peptides. One peptide, gp250, induced positive selection of AND CD4(+) T cells, had no homology with the AND TCR agonist ligand and was recognized with a high degree of specificity. The gp250 peptide acted as a coagonist to initiate the activation and enhance the survival of peripheral AND CD4(+) T cells. Thus, positively selecting ligands are critical in thymocyte development and in the activation and maintenance of peripheral T cells.

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