The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition
AuthorBorg, NA; Ely, LK; Beddoe, T; Macdonald, WA; Reid, HH; Clements, CS; Purcell, AW; Kjer-Nielsen, L; Miles, JJ; Burrows, SR; ...
Source TitleNATURE IMMUNOLOGY
PublisherNATURE PUBLISHING GROUP
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsBorg, N. A., Ely, L. K., Beddoe, T., Macdonald, W. A., Reid, H. H., Clements, C. S., Purcell, A. W., Kjer-Nielsen, L., Miles, J. J., Burrows, S. R., McCluskey, J. & Rossjohn, J. (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. https://doi.org/10.1038/ni1155.
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C1 - Journal Articles Refereed
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.
KeywordsCellular Immunology; Immune System and Allergy
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