Role of 2C T cell receptor residues in the binding of self- and allo- major histocompatibility complexes

Peter U.Y. Lee, Hywyn R.O. Churchill, Mark Daniels, Stephen C Jameson, David M. Kranz

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

T cell clone 2C recognizes the alloantigen L(d) and the positive selecting major histocompatibility complex (MHC), Kb. To explore the molecular basis of T cell antigen receptor (TCR) binding to different peptide/MHC (pMHC) complexes, we performed alanine scanning mutagenesis of the 2C TCR. The TCR energy maps for QL9/L(d) and SIYR/Kb were remarkably similar, in that 16 of 41 Vet and Vβ alanine mutants showed reduced binding to both ligands. Several TCR residues varied in the magnitude of energy contributed to binding the two ligands, indicating that there are also unique interactions. Residues in complementarity determining region 3α showed the most notable differences in binding energetics among the ligands QL9/L(d), SIYR/Kb, and the clonotypic antibody 1B2. Various lines of evidence suggest that these differences relate to the mobility of this loop and point to the key role of conformational dynamics in pMHC recognition.

Original languageEnglish (US)
Pages (from-to)1355-1364
Number of pages10
JournalJournal of Experimental Medicine
Volume191
Issue number8
DOIs
StatePublished - Apr 17 2000

Keywords

  • Alloantigen
  • Antigen recognition
  • Complementarity determining region
  • Peptide-major histocompatibility complex
  • T cell receptor

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