Nanobodies specific for Vβ11 enable detection and noninvasive imaging of antigen-specific T cells in vivo
- 29 August 2026
- journal article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 215 (9)
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
Funding Information
- National Multiple Sclerosis Society Career Transition Fellowship
- National Institutes of Health (R24OD035556)
- National Institutes of Health (R01CA255216)
- Lupus Research Alliance Innovative Award
- Charles H. Hood Foundation Child Health
- Rheumatology Research Foundation Innovative
- Boston Children’s Hospital Faculty Development and Pilot Grants
- Berlin Institute of Health
- American Heart Association Postdoctoral Fellowship
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