Detection of cell-cell interactions via photocatalytic cell tagging.
Nat Chem Biol, 2022/08;18(8):850-858.
Oslund RC[1, 2], Reyes-Robles T[3], White CH[4], Tomlinson JH[4], Crotty KA[4], Bowman EP[5], Chang D[6], Peterson VM[6], Li L[6], Frutos S[7], Vila-Perelló M[7], Vlerick D[8], Cromie K[8], Perlman DH[4], Ingale S[4], Hara SDO[4], Roberts LR[4], Piizzi G[4], Hett EC[4], Hazuda DJ[4, 9], Fadeyi OO[10, 11]
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PMID: 35654846DOI: 10.1038/s41589-022-01044-0
Impact factor: 16.174
Abstract
The growing appreciation of immune cell-cell interactions within disease environments has led to extensive efforts to develop immunotherapies. However, characterizing complex cell-cell interfaces in high resolution remains challenging. Thus, technologies leveraging therapeutic-based modalities to profile intercellular environments offer opportunities to study cell-cell interactions with molecular-level insight. We introduce photocatalytic cell tagging (PhoTag) for interrogating cell-cell interactions using single-domain antibodies (VHHs) conjugated to photoactivatable flavin-based cofactors. Following irradiation with visible light, the flavin photocatalyst generates phenoxy radical tags for targeted labeling. Using this technology, we demonstrate selective synaptic labeling across the PD-1/PD-L1 axis in antigen-presenting cell-T cell systems. In combination with multiomics single-cell sequencing, we monitored interactions between peripheral blood mononuclear cells and Raji PD-L1 B cells, revealing differences in transient interactions with specific T cell subtypes. The utility of PhoTag in capturing cell-cell interactions will enable detailed profiling of intercellular communication across different biological systems.
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