The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide-MHC recognition
- 9 January 2005
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 6 (2), 171-180
- https://doi.org/10.1038/ni1155
Abstract
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.Keywords
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