![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB |
![[thumbnail of Supplementary Information]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Information)
7MB |
| Item Type: | Article |
|---|---|
| Title: | Mice with a diverse human T cell receptor repertoire selected on multiple HLA class I molecules |
| Creators Name: | Dhamodaran, A., Chen, X., Fellmer, N., Agrawal, D., Danner, E., Kühn, R. and Blankenstein, T. |
| Abstract: | T cell receptor (TCR) gene therapy is an effective cancer treatment. Ideally, the TCR should be of human origin and have optimal avidity, e.g., isolated from a tumor antigen-non-tolerant host. Previously, we developed ABab-A2 mice which carry human TCRα and TCRβ gene loci and the human leukocyte antigen class I gene HLA-A*02:01 and are deficient for the corresponding mouse genes. Into these mice, we here introduce by PiggyBac transposon HLA-A*03:01, -A*11:01, -B*07:02, -B*15:01, -C*04:01, and -C*07:02 genes. These mice, termed ABab-I, exhibit increased peripheral CD8+ T cell counts and a higher CD8/CD4 ratio compared to ABab-A2 mice. ABab-I mice display a broader TCR repertoire with more unique V(D)J-TCRß clonotypes than ABab-A2 mice. Multi-HLA-I expression selected, on average, TCR with longer complementary determining region 3 (CDR3) compared to expression of a single HLA-I. ABab-I mice mount robust immune responses against viral, tumor-associated, and tumor-specific antigens. ABab-I mice allow simultaneous epitope and TCR discovery with broad HLA coverage, which could increase the number of cancer patients amenable to TCR-T treatments. |
| Keywords: | Alpha-Beta T-Cell Antigen Receptors, CD8-Positive T-Lymphocytes, Histocompatibility Antigens Class I, T-Cell Antigen Receptors, Transgenic Mice, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 5432 |
| Date: | 1 July 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-61306-y |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
