T cell recognition of hapten. Anatomy of T cell receptor binding of a H-2kd-associated photoreactive peptide derivative

J Biol Chem. 1999 Feb 5;274(6):3622-31. doi: 10.1074/jbc.274.6.3622.

Abstract

To elucidate the structural basis of T cell recognition of hapten-modified antigenic peptides, we studied the interaction of the T1 T cell antigen receptor (TCR) with its ligand, the H-2Kd-bound Plasmodium berghei circumsporozoite peptide 252-260 (SYIPSAEKI) containing photoreactive 4-azidobenzoic acid (ABA) on P. berghei circumsporozoite Lys259. The photoaffinity-labeled TCR residue(s) were mapped as Tyr48 and/or Tyr50 of complementary determining region 2beta (CDR2beta). Other TCR-ligand contacts were identified by mutational analysis. Molecular modeling, based on crystallographic coordinates of closely related TCR and major histocompatibility complex I molecules, indicated that ABA binds strongly and specifically in a cavity between CDR3alpha and CDR2beta. We conclude that TCR expressing selective Vbeta and CDR3alpha sequences form a binding domain between CDR3alpha and CDR2beta that can accommodate nonpeptidic moieties conjugated at the C-terminal portion of peptides binding to major histocompatibility complex (MHC) encoded proteins.

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • H-2 Antigens / chemistry*
  • Haptens / immunology*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Peptide Mapping
  • Peptides / chemistry
  • Peptides / immunology*
  • Photoaffinity Labels
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • H-2 Antigens
  • H-2K(K) antigen
  • Haptens
  • Peptides
  • Photoaffinity Labels
  • Receptors, Antigen, T-Cell