Force-Regulated In Situ TCR-Peptide-Bound MHC Class II Kinetics Determine Functions of CD4+ T Cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jinsung HongCheng Zhu

Abstract

We have recently shown that two-dimensional (2D) and force-regulated kinetics of TCR-peptide-bound MHC class I (pMHC-I) interactions predict responses of CD8(+) T cells. To test whether these findings are applicable to CD4(+) T cells, we analyzed the in situ 3.L2 TCR-pMHC-II interactions for a well-characterized panel of altered peptide ligands on the T cell surface using the adhesion frequency assay with a micropipette and the thermal fluctuation and force-clamp assays with a biomembrane force probe. We found that the 2D effective TCR-pMHC-II affinity and off-rate correlate with, but better predict the T cell response than, the corresponding measurements with the surface plasmon resonance in three dimensions. The 2D affinity of the CD4 for MHC-II was very low, approaching the detection limit, making it one to two orders of magnitude lower than the affinity of CD8 for MHC-I. In addition, the signal-dependent cooperation between TCR and coreceptor for pMHC binding previously observed for CD8 was not observed for CD4. Interestingly, force elicited TCR-pMHC-II catch-slip bonds for agonists but slip-only bonds for antagonists, thereby amplifying the power of discrimination between altered peptide ligands. These results show that th...Continue Reading

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Citations

Feb 26, 2016·Frontiers in Immunology·Claire Hivroz, Michael Saitakis
Dec 5, 2015·Frontiers in Immunology·Michael HebeisenNathalie Rufer
Apr 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Peter JönssonDavid Klenerman
May 4, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yang LiuKhalid Salaita
Dec 16, 2016·Nature Communications·Ryan J MartinezBrian D Evavold
Oct 28, 2016·Scientific Reports·Zhenhai LiCheng Zhu
Sep 29, 2017·Molecular Biology of the Cell·Yunfeng ChenCheng Zhu
Sep 10, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lori BlanchfieldBrian D Evavold
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Sep 20, 2019·Nature Immunology·Cheng ZhuKaitao Li
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Nov 14, 2018·Nature Immunology·Jinsung HongCheng Zhu
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