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

Andrew W. Woodham; Stad H. Zeigler; Ella L. Zeyang; Stephen C. Kolifrath; Ross W. Cheloha; Mohammad Rashidian; Rodolfo J. Chaparro; Ronald D. Seidel; Scott J. Garforth; Jason L. Dearling; Maia Mesyngier; Phaneendra K. Duddempudi; Alan B. Packard; Steven C. Almo; Hidde L. Ploegh

doi:10.1038/s41592-020-0934-5

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

Andrew W. Woodham, Stad H. Zeigler, Ella L. Zeyang, Stephen C. Kolifrath, Ross W. Cheloha, Mohammad Rashidian, Rodolfo J. Chaparro, Ronald D. Seidel, Scott J. Garforth, Jason L. Dearling, Maia Mesyngier, Phaneendra K. Duddempudi, Alan B. Packard, Steven C. Almo, Hidde L. Ploegh

Biochemistry

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1025-1032
Number of pages	8
Journal	Nature Methods
Volume	17
Issue number	10
DOIs	https://doi.org/10.1038/s41592-020-0934-5
State	Published - Oct 1 2020

ASJC Scopus subject areas

Biotechnology
Biochemistry
Molecular Biology
Cell Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41592-020-0934-5

Cite this

Woodham, A. W., Zeigler, S. H., Zeyang, E. L., Kolifrath, S. C., Cheloha, R. W., Rashidian, M., Chaparro, R. J., Seidel, R. D., Garforth, S. J., Dearling, J. L., Mesyngier, M., Duddempudi, P. K., Packard, A. B., Almo, S. C., & Ploegh, H. L. (2020). In vivo detection of antigen-specific CD8⁺ T cells by immuno-positron emission tomography. Nature Methods, 17(10), 1025-1032. https://doi.org/10.1038/s41592-020-0934-5

Woodham, AW, Zeigler, SH, Zeyang, EL, Kolifrath, SC, Cheloha, RW, Rashidian, M, Chaparro, RJ, Seidel, RD, Garforth, SJ, Dearling, JL, Mesyngier, M, Duddempudi, PK, Packard, AB, Almo, SC & Ploegh, HL 2020, 'In vivo detection of antigen-specific CD8⁺ T cells by immuno-positron emission tomography', Nature Methods, vol. 17, no. 10, pp. 1025-1032. https://doi.org/10.1038/s41592-020-0934-5

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

abstract = "The immune system{\textquoteright}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.",

author = "Woodham, {Andrew W.} and Zeigler, {Stad H.} and Zeyang, {Ella L.} and Kolifrath, {Stephen C.} and Cheloha, {Ross W.} and Mohammad Rashidian and Chaparro, {Rodolfo J.} and Seidel, {Ronald D.} and Garforth, {Scott J.} and Dearling, {Jason L.} and Maia Mesyngier and Duddempudi, {Phaneendra K.} and Packard, {Alan B.} and Almo, {Steven C.} and Ploegh, {Hidde L.}",

note = "Funding Information: A.W.W. is supported by the Arnold O. Beckman Postdoctoral Fellowship. R.W.C. is supported in part by funding from the Cancer Research Institute Irvington Postdoctoral Fellowship. M.R. was supported by the National Institutes of Health (grant 1K22CA226040-01). H.L.P. is supported by the Lustgarten Foundation (award ID 388167). The laboratory of H.L.P. receives financial support in the form of a sponsored research agreement from VIR in the general area of immunity to flu virus. We acknowledge Cue Biopharma for partial support of this work. The synTac technology was developed with support provided by the National Institutes of Health (U01GM094665, U54GM094662, R01AI145024 and R01CA198095 to S.C.A.). We acknowledge the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology (to S.C.A.) and Janet & Martin Spatz and the Helen & Irving Spatz Foundation. Additional support provided by the Albert Einstein Macromolecular Therapeutics Development Facility, the Einstein-Rockefeller-CUNY Center for AIDS Research (P30AI124414) and the Albert Einstein Cancer Center (P30CA013330). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

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AU - Zeyang, Ella L.

AU - Kolifrath, Stephen C.

AU - Cheloha, Ross W.

AU - Rashidian, Mohammad

AU - Chaparro, Rodolfo J.

AU - Seidel, Ronald D.

AU - Garforth, Scott J.

AU - Dearling, Jason L.

AU - Mesyngier, Maia

AU - Duddempudi, Phaneendra K.

AU - Packard, Alan B.

AU - Almo, Steven C.

AU - Ploegh, Hidde L.

N1 - Funding Information: A.W.W. is supported by the Arnold O. Beckman Postdoctoral Fellowship. R.W.C. is supported in part by funding from the Cancer Research Institute Irvington Postdoctoral Fellowship. M.R. was supported by the National Institutes of Health (grant 1K22CA226040-01). H.L.P. is supported by the Lustgarten Foundation (award ID 388167). The laboratory of H.L.P. receives financial support in the form of a sponsored research agreement from VIR in the general area of immunity to flu virus. We acknowledge Cue Biopharma for partial support of this work. The synTac technology was developed with support provided by the National Institutes of Health (U01GM094665, U54GM094662, R01AI145024 and R01CA198095 to S.C.A.). We acknowledge the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology (to S.C.A.) and Janet & Martin Spatz and the Helen & Irving Spatz Foundation. Additional support provided by the Albert Einstein Macromolecular Therapeutics Development Facility, the Einstein-Rockefeller-CUNY Center for AIDS Research (P30AI124414) and the Albert Einstein Cancer Center (P30CA013330). Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

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