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.
The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, USA.
Peter J R
PJ
Ebert
Shan
S
Jiang
Jianming
J
Xie
Qi-Jing
QJ
Li
Mark M
MM
Davis
D000818:Animals; D002478:Cells, Cultured; D017637:Clonal Deletion; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D035683:MicroRNAs; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C529100:mirn181 microRNA, mouse