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

Lauren K Ely; Travis Beddoe; Craig S Clements; Jacqueline M Matthews; Anthony W Purcell; Lars Kjer-Nielsen; James McCluskey; Jamie Rossjohn

doi:10.1073/pnas.0600743103

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

Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6641-6. doi: 10.1073/pnas.0600743103. Epub 2006 Apr 14.

Authors

Lauren K Ely¹, Travis Beddoe, Craig S Clements, Jacqueline M Matthews, Anthony W Purcell, Lars Kjer-Nielsen, James McCluskey, Jamie Rossjohn

Affiliation

¹ Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.

Abstract

The underlying basis of major histocompatibility complex (MHC) restriction is unclear. Nevertheless, current data suggest that a common thermodynamic signature dictates alphabeta 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites
Entropy
Epstein-Barr Virus Nuclear Antigens / genetics
Epstein-Barr Virus Nuclear Antigens / metabolism
HLA-B Antigens / chemistry*
HLA-B Antigens / metabolism*
HLA-B8 Antigen
Humans
Hydrophobic and Hydrophilic Interactions
In Vitro Techniques
Ligands
Models, Molecular
Multiprotein Complexes
Peptide Fragments / genetics
Peptide Fragments / immunology
Peptide Fragments / metabolism
Protein Conformation
Receptors, Antigen, T-Cell, alpha-beta / chemistry*
Receptors, Antigen, T-Cell, alpha-beta / metabolism*
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Signal Transduction
Surface Plasmon Resonance
T-Lymphocytes, Cytotoxic / immunology
Thermodynamics
beta 2-Microglobulin / chemistry
beta 2-Microglobulin / metabolism

Substances

Epstein-Barr Virus Nuclear Antigens
HLA-B Antigens
HLA-B*08:01 antigen
HLA-B8 Antigen
Ligands
Multiprotein Complexes
Peptide Fragments
Receptors, Antigen, T-Cell, alpha-beta
Recombinant Proteins
beta 2-Microglobulin