T Cell Antigen Recognition and Discrimination by Electrochemiluminescence Imaging
Yajuan Yan
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorDr. Ping Zhou
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorLurong Ding
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Dr. Wei Hu
Kidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Chen
Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058 China
Liangzhu Laboratory, Zhejiang University, Hangzhou, 311121 China
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education Frontier Science Center for Brain Science & Brain-machine Integration, State Key Laboratory for Modern Optical Instrumentation, Key Laboratory for Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310012 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Bin Su
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorYajuan Yan
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorDr. Ping Zhou
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorLurong Ding
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Dr. Wei Hu
Kidney Disease Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Chen
Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058 China
Liangzhu Laboratory, Zhejiang University, Hangzhou, 311121 China
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Ministry of Education Frontier Science Center for Brain Science & Brain-machine Integration, State Key Laboratory for Modern Optical Instrumentation, Key Laboratory for Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310012 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Bin Su
Key Laboratory of Excited-State Materials of Zhejiang Province, Department of Chemistry, Zhejiang University, Hangzhou, 310058 China
Search for more papers by this authorGraphical Abstract
We report a label-free approach for imaging immune synapses of T cells by electrochemiluminescence microscopy, which allows us to discriminate specific T cell receptor (TCR)/peptide-loaded major histocompatibility complex (pMHC) recognition, as well as the role of auxiliary molecules (costimulatory and adhesion molecules). The results would be useful in the development of tumour vaccines and adoptive T cell transfer immunotherapy.
Abstract
Adoptive T lymphocyte (T cell) transfer and tumour-specific peptide vaccines are innovative cancer therapies. An accurate assessment of the specific reactivity of T cell receptors (TCRs) to tumour antigens is required because of the high heterogeneity of tumour cells and the immunosuppressive tumour microenvironment. In this study, we report a label-free electrochemiluminescence (ECL) imaging approach for recognising and discriminating between TCRs and tumour-specific antigens by imaging the immune synapses of T cells. Various T cell stimuli, including agonistic antibodies, auxiliary molecules, and tumour-specific antigens, were modified on the electrode's surface to allow for their interaction with T cells bearing different TCRs. The formation of immune synapses activated by specific stimuli produced a negative (shadow) ECL image, from which T cell antigen recognition and discrimination were evaluated by analysing the spreading area and the recognition intensity of T cells. This approach provides an easy way to assess TCR-antigen specificity and screen both of them for immunotherapies.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
author upon reasonable request.
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References
- 1H. Sung, J. Ferlay, R. L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Ca-Cancer J. Clin. 2021, 71, 209.
- 2
- 2aD. S. Keller, M. Berho, R. O. Perez, S. D. Wexner, M. Chand, Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 414;
- 2bM.-Y. Li, L.-Z. Liu, M. Dong, Mol. Cancer 2021, 20, 22.
- 3A. D. Waldman, J. M. Fritz, M. J. Lenardo, Nat. Rev. Immunol. 2020, 20, 651.
- 4N. P. Restifo, M. E. Dudley, S. A. Rosenberg, Nat. Rev. Immunol. 2012, 12, 269.
- 5J. B. Huppa, M. Axmann, M. A. Mörtelmaier, B. F. Lillemeier, E. W. Newell, M. Brameshuber, L. O. Klein, G. J. Schütz, M. M. Davis, Nature 2010, 463, 963.
- 6
- 6aY. Hu, V. P.-Y. Ma, R. Ma, W. Chen, Y. Duan, R. Glazier, B. G. Petrich, R. Li, K. Salaita, Angew. Chem. Int. Ed. 2021, 60, 18044;
- 6bP. Friedl, A. T. den Boer, M. Gunzer, Nat. Rev. Immunol. 2005, 5, 532;
- 6cS. Čemerski, A. Shaw, Curr. Opin. Immunol. 2006, 18, 298.
- 7
- 7aE. Kobayashi, A. Jin, H. Hamana, K. Shitaoka, K. Tajiri, S. Kusano, S. Yokoyama, T. Ozawa, T. Obata, A. Muraguchi, H. Kishi, Nat. Biomed. Eng. 2022, 6, 806;
- 7bH. Liu, H. Luo, Q. Xue, S. Qin, S. Qiu, S. Liu, J. Lin, J. P. Li, P. R. Chen, J. Am. Chem. Soc. 2022, 144, 5517;
- 7cM. Nami, P. Han, D. Hanlon, K. Tatsuno, B. Wei, O. Sobolev, M. Pitruzzello, A. Vassall, S. Yosinski, R. Edelson, M. Reed, Adv. Mater. 2022, 34, 2109661;
- 7dK. Zhang, Y. Ma, D. Wang, J. Liu, J. An, Y. Li, C. Ma, Y. Pei, Z. Zhang, J. Liu, J. Shi, Nano Lett. 2022, 22, 1937.
- 8R. A. Subbramanian, C. Moriya, K. L. Martin, F. W. Peyerl, A. Hasegawa, A. Naoi, H. Chhay, P. Autissier, D. A. Gorgone, M. A. Lifton, K. Kuus-Reichel, J. E. Schmitz, N. L. Letvin, M. J. Kuroda, Nat. Biotechnol. 2004, 22, 1429.
- 9J. F. Ashby, J. Schmidt, N. Kc, A. Kurum, C. Koch, A. Harari, L. Tang, S. H. Au, Adv. Healthcare Mater. 2022, 11, 2200169.
- 10L. V. Sibener, R. A. Fernandes, E. M. Kolawole, C. B. Carbone, F. Liu, D. McAffee, M. E. Birnbaum, X. Yang, L. F. Su, W. Yu, S. Dong, M. H. Gee, K. M. Jude, M. M. Davis, J. T. Groves, W. A. Goddard, J. R. Heath, B. D. Evavold, R. D. Vale, K. C. Garcia, Cell 2018, 174, 672.
- 11
- 11aS. Viganò, D. T. Utzschneider, M. Perreau, G. Pantaleo, D. Zehn, A. Harari, Clin. Dev. Immunol. 2012, 2012, 153863;
- 11bS. Čemerski, J. Das, E. Giurisato, M. A. Markiewicz, P. M. Allen, A. K. Chakraborty, A. S. Shaw, Immunity 2008, 29, 414.
- 12A. Siokis, P. A. Robert, P. Demetriou, M. L. Dustin, M. Meyer-Hermann, Cell Rep. 2018, 24, 1151.
- 13W. E. Paul, R. A. Seder, Cell 1994, 76, 241.
- 14L. Balagopalan, E. Sherman, V. A. Barr, L. E. Samelson, Nat. Rev. Immunol. 2011, 11, 21.
- 15E. H. Doeven, E. M. Zammit, G. J. Barbante, C. F. Hogan, N. W. Barnett, P. S. Francis, Angew. Chem. Int. Ed. 2012, 51, 4354.
- 16H. Ding, W. Guo, P. Zhou, B. Su, Chem. Commun. 2020, 56, 8249.
- 17T.-B. Gao, J.-J. Zhang, J. Wen, X.-X. Yang, H.-B. Ma, D.-K. Cao, D. Jiang, Anal. Chem. 2020, 92, 1268.
- 18
- 18aF. Deiss, C. N. LaFratta, M. Symer, T. M. Blicharz, N. Sojic, D. R. Walt, J. Am. Chem. Soc. 2009, 131, 6088;
- 18bY. Wang, J. Ding, P. Zhou, J. Liu, Z. Qiao, K. Yu, J. Jiang, B. Su, Angew. Chem. Int. Ed. 2023, 62, e202216525.
- 19J. Dong, Y. Xu, Z. Zhang, J. Feng, Angew. Chem. Int. Ed. 2022, 61, e202200187.
- 20
- 20aH. Ding, P. Zhou, W. Fu, L. Ding, W. Guo, B. Su, Angew. Chem. Int. Ed. 2021, 60, 11769;
- 20bB. Li, X. Huang, Y. Lu, Z. Fan, B. Li, D. Jiang, N. Sojic, B. Liu, Adv. Sci. 2022, 9, 2204715;
- 20cG. Valenti, S. Scarabino, B. Goudeau, A. Lesch, M. Jović, E. Villani, M. Sentic, S. Rapino, S. Arbault, F. Paolucci, N. Sojic, J. Am. Chem. Soc. 2017, 139, 16830;
- 20dH. Ding, W. Guo, L. Ding, B. Su, Chin. J. Chem. 2021, 39, 2911.
- 21
- 21aY. Ma, C. Colin, J. Descamps, S. Arbault, N. Sojic, Angew. Chem. Int. Ed. 2021, 60, 18742;
- 21bJ. Descamps, C. Colin, G. Tessier, S. Arbault, N. Sojic, Angew. Chem. Int. Ed. 2023, 62, e202218574.
- 22
- 22aY. Liu, H. Zhang, B. Li, J. Liu, D. Jiang, B. Liu, N. Sojic, J. Am. Chem. Soc. 2021, 143, 17910;
- 22bN. Wang, H. Gao, Y. Li, G. Li, W. Chen, Z. Jin, J. Lei, Q. Wei, H. Ju, Angew. Chem. Int. Ed. 2021, 60, 197.
- 23
- 23aX. Hu, S. Yu, C. Wang, X. Zhang, J. Pan, H. Ju, Anal. Chem. 2023, 95, 4496;
- 23bS. Voci, B. Goudeau, G. Valenti, A. Lesch, M. Jović, S. Rapino, F. Paolucci, S. Arbault, N. Sojic, J. Am. Chem. Soc. 2018, 140, 14753.
- 24
- 24aL. Xu, Z. Zhou, C. Zhang, Y. He, B. Su, Chem. Commun. 2014, 50, 9097;
- 24bL. Xu, Y. Li, S. Wu, X. Liu, B. Su, Angew. Chem. Int. Ed. 2012, 51, 8068.
- 25
- 25aH. Ding, W. Guo, B. Su, Angew. Chem. Int. Ed. 2020, 59, 449;
- 25bL. Ding, H. Ding, P. Zhou, L. Xi, B. Su, Anal. Chem. 2022, 94, 10885.
- 26J. Zhang, S. Arbault, N. Sojic, D. Jiang, Annu. Rev. Anal. Chem. 2019, 12, 275.
- 27F. Yan, X. Lin, B. Su, Analyst 2016, 141, 3482.
- 28N. Kebede, P. S. Francis, G. J. Barbante, C. F. Hogan, Analyst 2015, 140, 7142.
- 29
- 29aW. Miao, J.-P. Choi, A. J. Bard, J. Am. Chem. Soc. 2002, 124, 14478;
- 29bM. Sentic, M. Milutinovic, F. Kanoufi, D. Manojlovic, S. Arbault, N. Sojic, Chem. Sci. 2014, 5, 2568;
- 29cA. Zanut, A. Fiorani, S. Canola, T. Saito, N. Ziebart, S. Rapino, S. Rebeccani, A. Barbon, T. Irie, H.-P. Josel, F. Negri, M. Marcaccio, M. Windfuhr, K. Imai, G. Valenti, F. Paolucci, Nat. Commun. 2020, 11, 2668;
- 29dW.-X. Fu, P. Zhou, W.-L. Guo, B. Su, Adv. Sens. Energy Mater. 2022, 1, 100028;
- 29eW. Guo, P. Zhou, L. Sun, H. Ding, B. Su, Angew. Chem. Int. Ed. 2021, 60, 2089.
- 30C. Ma, M.-X. Wang, H.-F. Wei, S. Wu, J.-R. Zhang, J.-J. Zhu, Z. Chen, Chem. Commun. 2021, 57, 2168.
- 31
- 31aM. A. Al-Aghbar, A. K. Jainarayanan, M. L. Dustin, S. R. Roffler, Commun. Biol. 2022, 5, 40;
- 31bS. Minguet, M. Swamy, B. Alarcón, I. F. Luescher, W. W. A. Schamel, Immunity 2007, 26, 43.
- 32L. Velas, M. Brameshuber, J. B. Huppa, E. Kurz, M. L. Dustin, P. Zelger, A. Jesacher, G. J. Schütz, Nano Lett. 2021, 21, 9247.
- 33
- 33aC. Ma, S. Wu, Y. Zhou, H.-F. Wei, J. Zhang, Z. Chen, J.-J. Zhu, Y. Lin, W. Zhu, Angew. Chem. Int. Ed. 2021, 60, 4907;
- 33bY. Chen, X. Gou, C. Ma, D. Jiang, J.-J. Zhu, Anal. Chem. 2021, 93, 7682.
- 34
- 34aJ. Oh, X. Xia, W. K. R. Wong, S. H. D. Wong, W. Yuan, H. Wang, C. H. N. Lai, Y. Tian, Y.-P. Ho, H. Zhang, Y. Zhang, G. Li, Y. Lin, L. Bian, Small 2022, 18, 2107373;
- 34bK. T. Bashour, A. Gondarenko, H. Chen, K. Shen, X. Liu, M. Huse, J. C. Hone, L. C. Kam, Proc. Natl. Acad. Sci. USA 2014, 111, 2241.
- 35
- 35aJ. Deeg, M. Axmann, J. Matic, A. Liapis, D. Depoil, J. Afrose, S. Curado, M. L. Dustin, J. P. Spatz, Nano Lett. 2013, 13, 5619;
- 35bD. Delcassian, D. Depoil, D. Rudnicka, M. Liu, D. M. Davis, M. L. Dustin, I. E. Dunlop, Nano Lett. 2013, 13, 5608;
- 35cH. Cai, J. Muller, D. Depoil, V. Mayya, M. P. Sheetz, M. L. Dustin, S. J. Wind, Nat. Nanotechnol. 2018, 13, 610.
- 36R. J. Brownlie, R. Zamoyska, Nat. Rev. Immunol. 2013, 13, 257.
- 37V. P.-Y. Ma, Y. Hu, A. V. Kellner, J. M. Brockman, A. Velusamy, A. T. Blanchard, B. D. Evavold, R. Alon, K. Salaita, Sci. Adv. 2022, 8, eabg4485.
- 38P. Nordenfelt, H. L. Elliott, T. A. Springer, Nat. Commun. 2016, 7, 13119.
- 39
- 39aA. Wahl, C. Dinet, P. Dillard, A. Nassereddine, P.-H. Puech, L. Limozin, K. Sengupta, Proc. Natl. Acad. Sci. USA 2019, 116, 5908;
- 39bJ. Huang, P.-F. Lo, T. Żal, N. R. J. Gascoigne, B. A. Smith, S. D. Levin, H. M. Grey, Proc. Natl. Acad. Sci. USA 2002, 99, 9369.
- 40E. Palmer, D. Naeher, Nat. Rev. Immunol. 2009, 9, 207.
- 41R. N. Germain, I. Stefanová, Annu. Rev. Immunol. 1999, 17, 467.
- 42
- 42aM. Aleksic, O. Dushek, H. Zhang, E. Shenderov, J.-L. Chen, V. Cerundolo, D. Coombs, P. A. van der Merwe, Immunity 2010, 32, 163;
- 42bJ.-L. Chen, P. R. Dunbar, U. Gileadi, E. Jäger, S. Gnjatic, Y. Nagata, E. Stockert, D. L. Panicali, Y.-T. Chen, A. Knuth, L. J. Old, V. Cerundolo, J. Immunol. 2000, 165, 948.
- 43L. Wang, X. Lan, Cell Discov. 2022, 8, 30.
- 44A. Poole, V. Karuppiah, A. Hartt, J. N. Haidar, S. Moureau, T. Dobrzycki, C. Hayes, C. Rowley, J. Dias, S. Harper, K. Barnbrook, M. Hock, C. Coles, W. Yang, M. Aleksic, A. B. Lin, R. Robinson, J. D. Dukes, N. Liddy, M. Van der Kamp, G. D. Plowman, A. Vuidepot, D. K. Cole, A. D. Whale, C. Chillakuri, Nat. Commun. 2022, 13, 5333.
- 45H. Colin-York, S. Kumari, L. Barbieri, L. Cords, M. Fritzsche, J. Cell Sci. 2020, 133, jcs232322.
- 46L. A. Colf, A. J. Bankovich, N. A. Hanick, N. A. Bowerman, L. L. Jones, D. M. Kranz, K. C. Garcia, Cell 2007, 129, 135.
- 47Y. Lu, X. Huang, S. Wang, B. Li, B. Liu, ACS Nano 2023, 17, 3809.
- 48
- 48aM.-M. Chen, C.-H. Xu, W. Zhao, H.-Y. Chen, J.-J. Xu, J. Am. Chem. Soc. 2021, 143, 18511;
- 48bJ. Dong, Y. Lu, Y. Xu, F. Chen, J. Yang, Y. Chen, J. Feng, Nature 2021, 596, 244;
- 48cY. Zhou, J. Dong, P. Zhao, J. Zhang, M. Zheng, J. Feng, J. Am. Chem. Soc. 2023, 145, 8947.
- 49J. Xu, P. Huang, Y. Qin, D. Jiang, H.-Y. Chen, Anal. Chem. 2016, 88, 4609.
