The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition

Borg, Natalie A., Ely, Lauren K., Beddoe, Travis, Macdonald, Whitney A., Reid, Hugh H., Clements, Craig S., Purcell, Anthony W., Kjer-Nielsen, Lars, Miles, John J., Burrows, Scott R., McCluskey, James, and Rossjohn, Jamie (2005) The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition. Nature Immunology, 6 (2). pp. 171-180.

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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 αβ 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.

Item ID: 45426
Item Type: Article (Research - C1)
ISSN: 1529-2916
Funders: Wellcome Trust, University of Melbourne, National Health and Medical Research Council of Australia (NHMRC), Australian Research Council (ARC), Roche Organ Transplantation Research Fund, Juvenile Diabetes Research Foundation
Date Deposited: 07 Sep 2016 02:12
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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