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| Item Type: | Article |
|---|---|
| Title: | Nanobodies specific for Vβ11 enable detection and noninvasive imaging of antigen-specific T cells in vivo |
| Creators: |
Scharmann, Stephanie D.  ORCID: https://orcid.org/0009-0003-5347-228X, Faber, Francisca, Hoorens van Heyningen, Lauren, Reljić, Mirna, Huisman, Brooke D., Faas, Priscilla P.M., Medhi, Himadri, Meyer, Manpreet ORCID: https://orcid.org/0009-0004-5700-8529, Gall, Camille Le, Sahay, Ishani, Suresh, Pavana, van Dalen, Floris J., Becht, Nanette, Ludwig, Leif S. ORCID: https://orcid.org/0000-0002-2916-2164, Birnbaum, Michael E. ORCID: https://orcid.org/0000-0002-2281-3518, Ploegh, Hidde L. and Pishesha, Novalia ORCID: https://orcid.org/0000-0002-8124-1265
|
| Abstract: | Through screening of a VHH phage display library constructed from an alpaca immunized with the recombinantly expressed murine myelin oligodendrocyte (MOG)-specific 2D2 T cell receptor (TCR), we identified nanobodies that reduced antigen-driven 2D2 T cell activation in vitro. Immunoblotting and staining confirmed TCRβ chain reactivity and Vβ11-associated recognition in polyclonal T cell populations. Site-specific sortase-mediated conjugation with desferrioxamine and 89Zr enabled nanobody-based immuno-PET/CT. In vivo imaging showed tracer accumulation in secondary lymphoid organs in settings enriched for Vβ11-expressing 2D2 T cells. In mice symptomatic for experimental autoimmune encephalomyelitis that had received MOG-specific 2D2 T cells, we observed a spinal cord-associated signal. This corresponded to accumulation of transferred Vβ11-expressing 2D2 T cells within inflamed spinal cord tissue. Compared with full-length immunoglobulins and multimeric peptide-MHC reagents that primarily support ex vivo detection of antigen-specific T cells, TCR-specific nanobodies show rapid clearance and improved tissue penetration that favor high-contrast immuno-PET/CT imaging of defined T cell populations in vivo. |
| Keywords: | Antigen-Specific T Cells, Experimental Autoimmune Encephalomyelitis, Immuno-PET Imaging, Nanobody, TCR Variable Region, Animals, Mice |
| Source: | Journal of Immunology |
| ISSN: | 0022-1767 |
| Publisher: | American Association of Immunologists |
| Volume: | 215 |
| Number: | 9 |
| Page Range: | vkag237 |
| Date: | September 2026 |
| Official Publication: | https://doi.org/10.1093/jimmun/vkag237 |
| PubMed: | View item in PubMed |
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