| First Author | Burn TN | Year | 2022 |
| Journal | J Immunol | Volume | 209 |
| Issue | 5 | Pages | 938-949 |
| PubMed ID | 35948399 | Mgi Jnum | J:349573 |
| Mgi Id | MGI:7346023 | Doi | 10.4049/jimmunol.2001441 |
| Citation | Burn TN, et al. (2022) The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCRbeta and TCRalpha Genes and Influences Development of alphabeta T Cell Lineages. J Immunol 209(5):938-949 |
| abstractText | RAG1/RAG2 (RAG) endonuclease-mediated assembly of diverse lymphocyte Ag receptor genes by V(D)J recombination is critical for the development and immune function of T and B cells. The RAG1 protein contains a ubiquitin ligase domain that stabilizes RAG1 and stimulates RAG endonuclease activity in vitro. We report in this study that mice with a mutation that inactivates the Rag1 ubiquitin ligase in vitro exhibit decreased rearrangements and altered repertoires of TCRbeta and TCRalpha genes in thymocytes and impaired thymocyte developmental transitions that require the assembly and selection of functional TCRbeta and/or TCRalpha genes. These Rag1 mutant mice present diminished positive selection and superantigen-mediated negative selection of conventional alphabeta T cells, decreased genesis of invariant NK T lineage alphabeta T cells, and mature CD4(+) alphabeta T cells with elevated autoimmune potential. Our findings reveal that the Rag1 ubiquitin ligase domain functions in vivo to stimulate TCRbeta and TCRalpha gene recombination and influence differentiation of alphabeta T lineage cells, thereby establishing replete diversity of alphabeta TCRs and populations of alphabeta T cells while restraining generation of potentially autoreactive conventional alphabeta T cells. |
