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Nat Immunol. 2009 Nov;10(11):1162-9. doi: 10.1038/ni.1797. Epub 2009 Oct 4.

An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a.

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The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA.


Thymic positive selection is based on the interactions of T cell antigen receptors (TCRs) with self peptide-major histocompatibility complex (MHC) ligands, but the identity of selecting peptides for MHC class II-restricted TCRs and the functional consequences of this peptide specificity are not clear. Here we identify several endogenous self peptides that positively selected the MHC class II-restricted 5C.C7 TCR. The most potent of these also enhanced mature T cell activation, which supports the hypothesis that one function of positive selection is to produce T cells that can use particular self peptide-MHC complexes for activation and/or homeostasis. We also show that inhibiting the microRNA miR-181a resulted in maturation of T cells that overtly reacted toward these erstwhile positively selecting peptides. Therefore, miR-181a helps to guarantee the clonal deletion of particular moderate-affinity clones by modulating the TCR signaling threshold of thymocytes.

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