Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction

被引:47
作者
Ely, LK
Beddoe, T
Clements, CS
Matthews, JM
Purcell, AW
Kjer-Nielsen, L
McCluskey, J [1 ]
Rossjohn, J
机构
[1] Monash Univ, Prot Crystallog Unit, Dept Biochem & Mol Biol, Sch Biomed Sci, Clayton, Vic 3800, Australia
[2] Univ Sydney, Sch Mol & Microbial Biosci, Sydney, NSW 2006, Australia
[3] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia
[4] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia
关键词
immunodominance; energetics; cytotoxic T lymphocyte; microcalorimetry; Epstein-Barr virus;
D O I
10.1073/pnas.0600743103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The underlying basis of major histocompatibility complex (MHC) restriction is unclear. Nevertheless, current data suggest that a common thermodynamic signature dictates alpha beta T cell receptor (TcR) ligation. To evaluate whether this thermodynamic signature defines MIHC restriction, we have examined the thermodynamic basis of a highly characterized immunodominant TcR interacting with its cognate peptide-MHC-I ligand. Surprisingly, we observed this interaction to be governed by favorable enthalpic and entropic forces, which is in contrast to the prevailing generality, namely, enthalpically driven interactions combined with markedly unfavorable entropic forces. We conclude that extrinsic molecular factors, such as coreceptor ligation, conformational adjustments involved in TcR signaling, or constraints dictated by higher-order arrangement of ligated TcRs, might play a greater role in guiding MHC restriction than appreciated previously.
引用
收藏
页码:6641 / 6646
页数:6
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