| First Author | Shinzawa M | Year | 2026 |
| Journal | Nat Immunol | Volume | 27 |
| Issue | 4 | Pages | 786-798 |
| PubMed ID | 41555085 | Mgi Jnum | J:379179 |
| Mgi Id | MGI:8286917 | Doi | 10.1038/s41590-025-02411-4 |
| Citation | Shinzawa M, et al. (2026) Unraveling CD8 lineage decisions reveals that functionally distinct CD8(+) T cells are selected by different MHC-I thymic peptides. Nat Immunol |
| abstractText | Thymocytes signaled by T cell antigen receptors to undergo positive selection acquire different functional fates while migrating through the thymus, but how this occurs remains uncertain. We now report that encoding CD8 co-receptors in both Cd4 and Cd8 gene loci modulates major histocompatibility complex (MHC-I) class I T cell antigen receptor signaling duration to generate all potential CD8(+) T cell subsets. Strikingly, such mice revealed that functionally different CD8(+) T cells are selected by different MHC-I thymic peptides. Thymocytes signaled by beta5t-peptides produced by thymoproteasomes exclusively expressed in the thymic cortex invariably become cytotoxic CD8(+) T cells indicating their signaling ceases when thymocytes leave the cortex; whereas thymocytes signaled by nonbeta5t-peptides expressed throughout the thymus become either helper or innate memory CD8(+) T cells because their signaling persists or recurs outside the cortex. Thus, it is because of their different thymic distributions that different MHC-I peptides select functionally different CD8(+) T cells, integrating peptide specificity and CD8(+) T cell function during positive selection and thymocyte migration. |
