Selective contact during TCR recognition

Recent structural analysis of the peptide-MHC complex revealsthat an antigenic peptide binds to MHC in only one conformationand that side chains anchoring in the binding pocket would notcontact TCR. The identification of all the MHC-anchoring residueson an antigenic peptide is a prerequisite to understand howa given peptide interacts with the TCR. In a combination ofbinding analysis and model simulation, model peptide repressorcl 16–26 was shown to bind to I-E^k through four anchorresidues (Leu 18, Ile21, Glu23 and Lys26), a pattern found inmany l-E^k-binding peptides. TCR reactivity analysis clearlyindicates a great variation in the interaction with cl 16–26by T cells generated from different strains of l-E^k-bearingmice. Most of the T cells generated from A/J mice reacted withthe central region of cl 16–26, while there is a greatdiversity on the recognition of cl 16–26 by T cells fromC3H and B10.BR mice. Despite the diverse interactions with antigenicpeptide by these T cells, most TCR-I-Ek contacts are limitedto the central region of the I-E^k ß-chain. T cellsrecognizing only the N-terminal part of cl 16–26 werefound to contact I-E^k at nearly the same residues as T cellsinteracting with the C-terminal of cl 16–26. TCR-I-E^krecognition was apparently independent of TCR-cl 16–26contact. The discordant TCR-peptide and TCR-MHC interactionsmay represent a unique feature of TCR recognition.