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


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.

SUBMITTER: Liu B 

PROVIDER: S-EPMC3941036 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Liu Baoyu B   Zhong Shi S   Malecek Karolina K   Johnson Laura A LA   Rosenberg Steven A SA   Zhu Cheng C   Krogsgaard Michelle M  

European journal of immunology 20131020 1


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 melanom  ...[more]

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