| First Author | Klawon DEJ | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 6 | PubMed ID | 33914024 |
| Mgi Jnum | J:316013 | Mgi Id | MGI:6724849 |
| Doi | 10.1084/jem.20200701 | Citation | Klawon DEJ, et al. (2021) Altered selection on a single self-ligand promotes susceptibility to organ-specific T cell infiltration. J Exp Med 218(6) |
| abstractText | For the large array of self-peptide/MHC class II (pMHC-II) complexes displayed in the body, it is unclear whether CD4+ T cell tolerance must be imparted for each individual complex or whether pMHC-II-nonspecific bystander mechanisms are sufficient to confer tolerance by acting broadly on T cells reactive to multiple self-pMHC-II ligands. Here, via reconstitution of T cell-deficient mice, we demonstrate that altered T cell selection on a single prostate-specific self-pMHC-II ligand renders recipient mice susceptible to prostate-specific T cell infiltration. Mechanistically, this self-pMHC-II complex is required for directing antigen-specific cells into the Foxp3+ regulatory T cell lineage but does not induce clonal deletion to a measurable extent. Thus, our data demonstrate that polyclonal T reg cells are unable to functionally compensate for a breach in tolerance to a single self-pMHC-II complex in this setting, revealing vulnerabilities in antigen-nonspecific bystander mechanisms of immune tolerance. |
