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T cells use distinct topographical and membrane receptor scanning strategies that individually coalesce during receptor recognition.

En CaiCasey BepplerJohn EichorstKyle MarchukScott W EastmanMatthew F Krummel
Published in: Proceedings of the National Academy of Sciences of the United States of America (2022)
During immune surveillance, CD8 T cells scan the surface of antigen-presenting cells using dynamic microvillar palpation and movements as well as by having their receptors preconcentrated into patches. Here, we use real-time lattice light-sheet microscopy to demonstrate the independence of microvillar and membrane receptor patch scanning. While T cell receptor (TCR) patches can distribute to microvilli, they do so stochastically and not preferentially as for other receptors such as CD62L. The distinctness of TCR patch movement from microvillar movement extends to many other receptors that form patches that also scan independent of the TCR. An exception to this is the CD8 coreceptor which largely comigrates in patches that overlap with or are closely adjacent to those containing TCRs. Microvilli that assemble into a synapse contain various arrays of the engaged patches, notably of TCRs and the inhibitory receptor PD-1, creating a pastiche of occupancies that vary from microvillar contact to contact. In summary, this work demonstrates that localization of receptor patches within the membrane and on microvillar projections is random prior to antigen detection and that such random variation may play into the generation of many individually composed receptor patch compositions at a single synapse.
Keyphrases
  • high resolution
  • computed tomography
  • public health
  • regulatory t cells
  • binding protein
  • magnetic resonance imaging
  • cell proliferation
  • optical coherence tomography
  • dendritic cells
  • high speed
  • quantum dots
  • single cell