The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCR β and TCRα Genes and Influences Development of αβ T Cell Lineages

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 TCRβ and TCRα genes in thymocytes and impaired thymocyte developmental transitions that require the assembly and selection of functional TCRβ and/or TCRα genes. These Rag1 mutant mice present diminished positive selection and superantigen-mediated negative selection of conventional αβ T cells, decreased genesis of invariant NK T lineage αβ T cells, and mature CD4+ αβ T cells with elevated autoimmune potential. Our findings reveal that the Rag1 ubiquitin ligase domain functions in vivo to stimulate TCRβ and TCRα gene recombination and influence differentiation of αβ T lineage cells, thereby establishing replete diversity of αβ TCRs and populations of αβ T cells while restraining generation of potentially autoreactive conventional αβ T cells.PMID:35948399 | DOI:10.4049/jimmunol.2001441
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research