On defining the rules for interactions between the T cell receptor and its ligand: A critical role for a specific amino acid residue of the T cell receptor β chain

Fuming Wang, Toshiro Ono, Alexis M. Kalergis, Weijia Zhang, Teresa P. DiLorenzo, Kap Lim, Stanley G. Nathenson

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The specificity of T cell-mediated immune responses is primarily determined by the interaction between the T cell receptor (TCR) and the antigenic peptide presented by the major histocompatibility complex (MHC) molecules. To refine our understanding of interactions between the TCR and the antigenic peptide of vesicular stomatitis virus (VSV) presented by the class I MHC molecule H-2K(b), we constructed a TCR α chain transgenic mouse in a TCR α-deficient background to define specific structural features in the TCR β chain that are important for the recognition of the VSV/H-2K(b) complex. We found that for a given peptide, a peptide-specific, highly conserved amino acid could always be identified at position 98 of the complementarity-determining region 3 (CDR3) loop of TCR β chains. Further, we demonstrated that substitutions at position 6, but not position 1, of the VSV peptide induced compensatory changes in the TCR in both the amino acid residue at position 98 and the length of the CDR3β loop. We conclude that the amino acid residue at position 98 of the CDR3β loop is a key residue that plays a critical role in determining the specificity of TCR-VSV/H-2K(b) interactions and that a specific length of the CDR3β loop is required to facilitate such interactions. Further, these findings suggest that the α and β chains of TCRs interact with amino acid residue(s) toward then and C termini of the VSV peptide, respectively, providing functional evidence for the orientation of a TCR with its peptide/MHC ligand as observed in the crystal structures of TCR/peptide/MHC complexes.

Original languageEnglish
Pages (from-to)5217-5222
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number9
DOIs
Publication statusPublished - Apr 28 1998

ASJC Scopus subject areas

  • General

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