期刊
JOURNAL OF IMMUNOLOGY
卷 187, 期 12, 页码 6281-6290出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1101734
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资金
- National Institutes of Health [P01 CA097296, R01 GM55767, PO1-AI071195]
- Cancer Center
- Samuel and Ruth Engelberg/Irvington Institute, Cancer Research Institute
The binding of oligomeric peptide-MHC (pMHC) complexes to cell surface TCR can be considered to approximate TCR-pMHC interactions at cell-cell interfaces. In this study, we analyzed the equilibrium binding of streptavidin-based pMHC oligomers (tetramers) and their dissociation kinetics from CD8(pos) T cells from 2C-TCR transgenic mice and from T cell hybridomas that expressed the 2C TCR or a high-affinity mutant (m33) of this TCR. Our results show that the tetramers did not come close to saturating cell-surface TCR (binding only 10-30% of cell-surface receptors), as is generally assumed in deriving affinity values (K(D)), in part because of dissociative losses from tetramer-stained cells. Guided by a kinetic model, the oligomer dissociation rate and equilibrium constants were seen to depend not only on monovalent association and dissociation rates (k(off) and k(on)), but also on a multivalent association rate (mu) and TCR cell-surface density. Our results suggest that dissociation rates could account for the recently described surprisingly high frequency of tetramer-negative, functionally competent T cells in some T cell responses. The Journal of Immunology, 2011, 187: 6281-6290.
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