Nature Immunology6, 171 - 180 (2005)
Published online: 9 January 2005; | doi:10.1038/ni1155
The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition
Natalie A Borg1, 4, Lauren K Ely1, 4, Travis Beddoe1, Whitney A Macdonald1, Hugh H Reid1, Craig S Clements1, Anthony W Purcell2, Lars Kjer-Nielsen2, John J Miles3, Scott R Burrows3, James McCluskey2
& Jamie Rossjohn1
1
The Protein Crystallography Unit, Monash Centre for Synchrotron Science, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
2
Department of Microbiology & Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
3
Cellular Immunology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia.
The energetic bases of T cell recognition are unclear. Here, we studied the 'energetic landscape' of peptide−major histocompatibility complex (pMHC) recognition by an immunodominant T cell receptor (TCR). We quantified and evaluated the effect of natural and systematic substitutions in the complementarity-determining region (CDR) loops on ligand binding in the context of the structural detail of each component of the immunodominant TCR-pMHC complex. The CDR1 and CDR2 loops contributed minimal energy through direct recognition of the antigen and instead had a chief function in stabilizing the ligated CDR3 loops. The underlying energetic basis for recognition lay in the CDR3 loops. Therefore the energetic burden of the CDR loops in the TCR-pMHC interaction is variable among TCRs, reflecting the inherent adaptability of the TCR in ligating different ligands.
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T cell receptor (TCR). We quantified and evaluated the effect of natural and systematic substitutions in the complementarity-determining region (CDR) loops on ligand binding in the context of the structural detail of each component of the immunodominant TCR-pMHC complex. The CDR1 and CDR2 loops contributed minimal energy through direct recognition of the antigen and instead had a chief function in stabilizing the ligated CDR3 loops. The underlying energetic basis for recognition lay in the CDR3 loops. Therefore the energetic burden of the CDR loops in the TCR-pMHC interaction is variable among TCRs, reflecting the inherent adaptability of the TCR in ligating different ligands.
