In vivo detection of antigen-specific CD8+T cells by immuno-positron emission tomography

被引:33
|
作者
Woodham, Andrew W. [1 ,2 ]
Zeigler, Stad H. [3 ]
Zeyang, Ella L. [9 ]
Kolifrath, Stephen C. [1 ,2 ]
Cheloha, Ross W. [1 ,2 ]
Rashidian, Mohammad [5 ]
Chaparro, Rodolfo J. [6 ]
Seidel, Ronald D. [6 ]
Garforth, Scott J. [3 ]
Dearling, Jason L. [7 ]
Mesyngier, Maia [1 ,4 ]
Duddempudi, Phaneendra K. [3 ]
Packard, Alan B. [8 ]
Almo, Steven C. [2 ]
Ploegh, Hidde L. [1 ,2 ]
机构
[1] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA
[3] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10467 USA
[4] MIT, Dept Biol, Cambridge, MA USA
[5] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA
[6] Cue Biopharma, Cambridge, MA USA
[7] Childrens Hosp, Dept Radiol, Div Nucl Med, 300 Longwood Ave, Boston, MA 02115 USA
[8] Harvard Med Sch, Boston Childrens Hosp, Nucl Med & Mol Imaging, Boston, MA 02115 USA
[9] MIT, Dept Biol, Cambridge, MA USA
基金
美国国家卫生研究院;
关键词
SUBDOMINANT EPITOPE; VIRAL PEPTIDES; FC-RECEPTOR; VACCINATION; HPV; RECOGNITION; EXPRESSION; ANTIBODIES; PROTEIN; TARGET;
D O I
10.1038/s41592-020-0934-5
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The immune system's ability to recognize peptides on major histocompatibility molecules contributes to the eradication of cancers and pathogens. Tracking these responses in vivo could help evaluate the efficacy of immune interventions and improve mechanistic understanding of immune responses. For this purpose, we employ synTacs, which are dimeric major histocompatibility molecule scaffolds of defined composition. SynTacs, when labeled with positron-emitting isotopes, can noninvasively image antigen-specific CD8(+)T cells in vivo. Using radiolabeled synTacs loaded with the appropriate peptides, we imaged human papillomavirus-specific CD8(+)T cells by positron emission tomography in mice bearing human papillomavirus-positive tumors, as well as influenza A virus-specific CD8(+)T cells in the lungs of influenza A virus-infected mice. It is thus possible to visualize antigen-specific CD8(+)T-cell populations in vivo, which may serve prognostic and diagnostic roles. Antigen-specific CD8(+)T cells can be imaged by immunoPET with the help of synTacs, MHC-based tools that bind to relevant T-cell receptors.
引用
收藏
页码:1025 / +
页数:14
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