| First Author | Tritz ZP | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 5 | Pages | 1228-1238 |
| PubMed ID | 32737149 | Mgi Jnum | J:301438 |
| Mgi Id | MGI:6502395 | Doi | 10.4049/jimmunol.2000340 |
| Citation | Tritz ZP, et al. (2020) Conditional Silencing of H-2D(b) Class I Molecule Expression Modulates the Protective and Pathogenic Kinetics of Virus-Antigen-Specific CD8 T Cell Responses during Theiler's Virus Infection. J Immunol 205(5):1228-1238 |
| abstractText | Theiler's murine encephalomyelitis virus (TMEV) infection of the CNS is cleared in C57BL/6 mice by a CD8 T cell response restricted by the MHC class I molecule H-2D(b) The identity and function of the APC(s) involved in the priming of this T cell response is (are) poorly defined. To address this gap in knowledge, we developed an H-2D(b) LoxP-transgenic mouse system using otherwise MHC class I-deficient C57BL/6 mice, thereby conditionally ablating MHC class I-restricted Ag presentation in targeted APC subpopulations. We observed that CD11c(+) APCs are critical for early priming of CD8 T cells against the immunodominant TMEV peptide VP2121-130 Loss of H-2D(b) on CD11c(+) APCs mitigates the CD8 T cell response, preventing early viral clearance and immunopathology associated with CD8 T cell activity in the CNS. In contrast, animals with H-2D(b)-deficient LysM(+) APCs retained early priming of D(b):VP2121-130 epitope-specific CD8 T cells, although a modest reduction in immune cell entry into the CNS was observed. This work establishes a model enabling the critical dissection of H-2D(b)-restricted Ag presentation to CD8 T cells, revealing cell-specific and temporal features involved in the generation of CD8 T cell responses. Employing this novel system, we establish CD11c(+) cells as pivotal to the establishment of acute antiviral CD8 T cell responses against the TMEV immunodominant epitope VP2121-130, with functional implications both for T cell-mediated viral control and immunopathology. |
