Differential roles of T cell receptor α and β chains in ligand binding among H-2K(d)-restricted cytolytic T lymphocyte clones specific for a photoreactive Plasmodium berghei circumsporozoite peptide derivative

Fabienne Anjuère, Dmitry Kuznetsov, Pedro Romero, Jean Charles Cerottini, C. Victor Jongeneel, Immanuel F. Luescher

Research output: Contribution to journalArticlepeer-review

Abstract

To study the interaction of T cell receptor with its ligand, a complex of a major histocompatibility complex molecule and a peptide, we derived H- 2K(d)-restricted cytolytic T lymphocyte clones from mice immunized with a Plasmodium berghei circumsporozoite peptide (PbCS) 252-260 (SYIPSAEKI) derivative containing photoreactive N(ε)-[4-azidobenzoyl] lysine in place of Pro-255. This residue and Lys-259 were essential parts of the epitope recognized by these clones. Most of the clones expressed BV1S1A1 encoded β chains along with specific complementary determining region (CDR) 3β regions but diverse α chain sequences. Surprisingly, all T cell receptors were preferentially photoaffinity labeled on the chain. For a representative T cell receptor, the photoaffinity labeled site was located in the Vα C- strand. Computer modeling suggested the presence of a hydrophobic pocket, which is formed by parts of the Vα/Jα C-, F-, and G-strands and adjacent CDR3α residues and structured to be able to avidly bind the photoreactive ligand side chain. We previously found that a T cell receptor specific for a PbCS peptide derivative containing this photoreactive side chain in position 259 similarly used a hydrophobic pocket located between the junctional CDR3 loops. We propose that this nonpolar domain in these locations allow T cell receptors to avidly and specifically bind epitopes containing non-peptidic side chains.

Original languageEnglish (US)
Pages (from-to)8505-8514
Number of pages10
JournalJournal of Biological Chemistry
Volume272
Issue number13
DOIs
StatePublished - Mar 28 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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