2D TCR-pMHC-CD8 kinetics determines T-cell responses in a self-antigen-specific TCR system

Baoyu Liu, Shi Zhong, Karolina Malecek, Laura A. Johnson, Steven A. Rosenberg, Cheng Zhu, Michelle Krogsgaard

Research output: Contribution to journalArticle

Abstract

Two-dimensional (2D) kinetic analysis directly measures molecular interactions at cell-cell junctions, thereby incorporating inherent cellular effects. By comparison, three-dimensional (3D) analysis probes the intrinsic physical chemistry of interacting molecules isolated from the cell. To understand how T-cell tumor reactivity relates to 2D and 3D binding parameters and to directly compare them, we performed kinetic analyses of a panel of human T-cell receptors (TCRs) interacting with a melanoma self-antigen peptide (gp100209-217) bound to peptide-major histocompatibility complex in the absence and presence of co-receptor CD8. We found that while 3D parameters are inadequate to predict T-cell function, 2D parameters (that do not correlate with their 3D counterparts) show a far broader dynamic range and significantly improved correlation with T-cell function. Thus, our data support the general notion that 2D parameters of TCR-peptide-major histocompatibility complex-CD8 interactions determine T-cell responsiveness and suggest a potential 2D-based strategy to screen TCRs for tumor immunotherapy.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalEuropean Journal of Immunology
Volume44
Issue number1
DOIs
StatePublished - Jan 2014

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Keywords

  • 2D kinetics
  • Micropipette adhesion frequency assay
  • T-cell activation
  • Thermal fluctuation assay

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Liu, B., Zhong, S., Malecek, K., Johnson, L. A., Rosenberg, S. A., Zhu, C., & Krogsgaard, M. (2014). 2D TCR-pMHC-CD8 kinetics determines T-cell responses in a self-antigen-specific TCR system. European Journal of Immunology, 44(1), 239-250. https://doi.org/10.1002/eji.201343774