Journal
NATURE IMMUNOLOGY
Volume 10, Issue 11, Pages 1162-U44Publisher
NATURE RESEARCH
DOI: 10.1038/ni.1797
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Funding
- Howard Hughes Medical Institute
- Duke University
- US National Institutes of Health [RO1 AIO22511]
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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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