Disparate Thermodynamics Governing T Cell Receptor-MHC-I Interactions Implicate Extrinsic Factors in Guiding MHC Restriction
The underlying basis of major histocompatibility complex (MHC) restriction is unclear. Nevertheless, current data suggest that a common thermodynamic signature dictates αβ T cell receptor (TcR) ligation. To evaluate whether this thermodynamic signature defines MHC restriction, we have examined the t...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 17; pp. 6641 - 6646 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
25.04.2006
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Subjects | |
Online Access | Get full text |
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Summary: | The underlying basis of major histocompatibility complex (MHC) restriction is unclear. Nevertheless, current data suggest that a common thermodynamic signature dictates αβ T cell receptor (TcR) ligation. To evaluate whether this thermodynamic signature defines MHC 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 L.K.E. and T.B. contributed equally to this work. Author contributions: J.M. and J.R. designed research; L.K.E. and T.B. performed research; J.M.M. contributed new reagents/analytical tools; L.K.E., T.B., C.S.C., A.W.P., L.K.-N., J.M., and J.R. analyzed data; and L.K.E., A.W.P., J.M., and J.R. wrote the paper. Present address: Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305. Communicated by Jacques F. A. P. Miller, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, February 16, 2006 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0600743103 |