An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a.
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.
Duke Scholars
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- Thymus Gland
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Peptides
- MicroRNAs
- Mice, Knockout
- Mice
- Lymphocyte Activation
- Immunology
- Histocompatibility Antigens Class II
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Peptides
- MicroRNAs
- Mice, Knockout
- Mice
- Lymphocyte Activation
- Immunology
- Histocompatibility Antigens Class II