Alanine scanning mutagenesis of an αβ T cell receptor: Mapping the energy of antigen recognition

Thomas C. Manning, Carol J. Schlueter, Thomas C. Brodnicki, Evan A. Parke, Jeffrey A. Speir, K. Christopher Garcia, Luc Teyton, Ian A. Wilson, David M. Kranz

Research output: Contribution to journalArticlepeer-review

Abstract

The T cell receptor (TCR) from the alloreactive T lymphocyte 2C recognizes a nonamer peptide QL9 complexed with the MHC class I molecule H2- L(d). Forty-two single-site alanine substitutions of the 2C TCR were analyzed for binding to QL9/L(d) and anti-TCR antibodies. The results provided a detailed energy map of T cell antigen recognition and indicated that the pMHC and clonotypic antibody epitopes on the TCR were similar. Although residues in each Vα and Vβ CDR are important in binding pMHC, the most significant energy for the TCR/QL9/L(d) interaction was contributed by CDRs I and 2 of both α and β chains. The extent to which the individual energy contributions are directed at class I helices or peptide was also assessed.

Original languageEnglish (US)
Pages (from-to)413-425
Number of pages13
JournalImmunity
Volume8
Issue number4
DOIs
StatePublished - Apr 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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