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

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Abstract
Endogenous peptides that positively select major histocompatibility complex class II-restricted T cell receptors have not yet been identified. Groups led by Davis and Allen identify several such peptides and find that they influence activation and homeostasis of peripheral T cells. 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-Ek-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.