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Immunoblotting and staining confirmed TCR\u03b2 chain reactivity and V\u03b211-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 V\u03b211-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 V\u03b211-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.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag237","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:40:08Z","timestamp":1788000008000},"source":"Crossref","is-referenced-by-count":0,"title":["Nanobodies specific for V\u03b211 enable detection and noninvasive imaging of antigen-specific T cells in vivo"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5347-228X","authenticated-orcid":false,"given":"Stephanie D","family":"Scharmann","sequence":"first","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA,","place":["United 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