Nov, 2009
The alpha beta T Cell Receptor Is an Anisotropic Mechanosensor
JOURNAL OF BIOLOGICAL CHEMISTRY
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- Volume
- 284
- Number
- 45
- First page
- 31028
- Last page
- 31037
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1074/jbc.M109.052712
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Thymus-derived lymphocytes protect mammalian hosts against virus- or cancer-related cellular alterations through immune surveillance, eliminating diseased cells. In this process, T cell receptors (TCRs) mediate both recognition and T cell activation via their dimeric alpha beta, CD3 epsilon gamma, CD3 epsilon delta, and CD3 zeta zeta subunits using an unknown structural mechanism. Here, site-specific binding topology of anti-CD3 monoclonal antibodies (mAbs) and dynamic TCR quaternary change provide key clues. Agonist mAbs footprint to the membrane distal CD3 epsilon lobe that they approach diagonally, adjacent to the lever-like C beta FG loop that facilitates antigen (pMHC)-triggered activation. In contrast, a non-agonist mAb binds to the cleft between CD3 epsilon and CD3 gamma in a perpendicular mode and is stimulatory only subsequent to an external tangential but not a normal force (similar to 50 piconewtons) applied via optical tweezers. Specific pMHC but not irrelevant pMHC activates a T cell upon application of a similar force. These findings suggest that the TCR is an anisotropic mechanosensor, converting mechanical energy into a biochemical signal upon specific pMHC ligation during immune surveillance. Activating anti-CD3 mAbs mimic this force via their intrinsic binding mode. A common TCR quaternary change rather than conformational alterations can better facilitate structural signal initiation, given the vast array of TCRs and their specific pMHC ligands.
- Link information
- ID information
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- DOI : 10.1074/jbc.M109.052712
- ISSN : 0021-9258
- Pubmed ID : 19755427
- Web of Science ID : WOS:000271378400032