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


  • 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
  • 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
  • Rossjohn, Jamie

publication date

  • February 2005