| First Author | Mori S | Year | 2024 |
| Journal | Cell | Volume | 187 |
| Issue | 21 | Pages | 6071-6087.e20 |
| PubMed ID | 39276775 | Mgi Jnum | J:358177 |
| Mgi Id | MGI:7779297 | Doi | 10.1016/j.cell.2024.08.025 |
| Citation | Mori S, et al. (2024) Neoself-antigens are the primary target for autoreactive T cells in human lupus. Cell 187(21):6071-6087.e20 |
| abstractText | Major histocompatibility complex class II (MHC-II) is the most significant genetic risk factor for systemic lupus erythematosus (SLE), but the nature of the self-antigens that trigger autoimmunity remains unclear. Unusual self-antigens, termed neoself-antigens, are presented on MHC-II in the absence of the invariant chain essential for peptide presentation. Here, we demonstrate that neoself-antigens are the primary target for autoreactive T cells clonally expanded in SLE. When neoself-antigen presentation was induced by deleting the invariant chain in adult mice, neoself-reactive T cells were clonally expanded, leading to the development of lupus-like disease. Furthermore, we found that neoself-reactive CD4(+) T cells were significantly expanded in SLE patients. A high frequency of Epstein-Barr virus reactivation is a risk factor for SLE. Neoself-reactive lupus T cells were activated by Epstein-Barr-virus-reactivated cells through downregulation of the invariant chain. Together, our findings imply that neoself-antigen presentation by MHC-II plays a crucial role in the pathogenesis of SLE. |
