Humanization of T cell-mediated immunity in mice.
| Title: | Humanization of T cell-mediated immunity in mice. |
|---|---|
| Authors: | Moore MJ; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Zhong M; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Hansen J; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Gartner H; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Grant C; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Huang M; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Harris FM; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Tu N; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Bowerman NA; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Edelmann KH; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Barry T; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Herbin O; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Tay CS; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; DiLillo DJ; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Decker CE; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Levenkova N; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Shevchuk J; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Dhanik A; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Meagher KA; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Karr A; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Roos J; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Lee WY; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Suh D; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Eckersdorff M; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Meagher TC; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Koss M; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Esau L; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Sleeman MA; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Babb R; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Chen G; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Kyratsous CA; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Poueymirou WT; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; McWhirter JR; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Voronina VA; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Guo C; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Gurer C; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Yancopoulos GD; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Murphy AJ; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA.; Macdonald LE; Regeneron Pharmaceuticals, 777 Old Saw Mill River Rd, Tarrytown, NY 10591, USA. |
| Source: | Science immunology [Sci Immunol] 2021 Dec 17; Vol. 6 (66), pp. eabj4026. Date of Electronic Publication: 2021 Dec 17. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101688624 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2470-9468 (Electronic) Linking ISSN: 24709468 NLM ISO Abbreviation: Sci Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science, [2016]- |
| MeSH Terms: | Receptors, Antigen, T-Cell, alpha-beta/*immunology ; T-Lymphocytes/*immunology; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Animals ; Humans ; Mice ; Mice, Inbred C57BL |
| Abstract: | Despite the enormous promise of T cell therapies, the isolation and study of human T cell receptors (TCRs) of dedicated specificity remains a major challenge. To overcome this limitation, we generated mice with a genetically humanized system of T cell immunity. We used VelociGene technology to replace the murine TCRαβ variable regions, along with regions encoding the extracellular domains of co-receptors CD4 and CD8, and major histocompatibility complex (MHC) class I and II, with corresponding human sequences. The resulting “VelociT” mice have normal myeloid and lymphoid immune cell populations, including thymic and peripheral αβ T cell subsets comparable with wild-type mice. VelociT mice expressed a diverse TCR repertoire, mounted functional T cell responses to lymphocytic choriomeningitis virus infection, and could develop experimental autoimmune encephalomyelitis. Immunization of VelociT mice with human tumor-associated peptide antigens generated robust, antigen-specific responses and led to identification of a TCR against tumor antigen New York esophageal squamous cell carcinoma-1 with potent antitumor activity. These studies demonstrate that VelociT mice mount clinically relevant T cell responses to both MHC-I– and MHC-II–restricted antigens, providing a powerful new model for analyzing T cell function in human disease. Moreover, VelociT mice are a new platform for de novo discovery of therapeutic human TCRs. |
| Substance Nomenclature: | 0 (Receptors, Antigen, T-Cell, alpha-beta) |
| Entry Date(s): | Date Created: 20211217 Date Completed: 20220307 Latest Revision: 20220307 |
| Update Code: | 20260130 |
| DOI: | 10.1126/sciimmunol.abj4026 |
| PMID: | 34919442 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't