The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition.
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 alphabeta 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.
Borg
Natalie A
NA
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.
Ely
Lauren K
LK
Beddoe
Travis
T
Macdonald
Whitney A
WA
Reid
Hugh H
HH
Clements
Craig S
CS
Purcell
Anthony W
AW
Kjer-Nielsen
Lars
L
Miles
John J
JJ
Burrows
Scott R
SR
McCluskey
James
J
Rossjohn
Jamie
J
D001483:Base Sequence; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
D022801:Complementarity Determining Regions; D006649:Histocompatibility Antigens; D008024:Ligands; D010455:Peptides; D011948:Receptors, Antigen, T-Cell