T cell recognition of hapten: Anatomy of T cell receptor binding of a H- 2K(d)-associated photoreactive peptide derivative

Benedikt Kessler, Olivier Michielin, Christopher L. Blanchard, Irina Apostolou, Christaiane Delarbre, Gabriel Gachelin, Claude Grégoire, Bernard Malissen, Jean Charles Cerottini, Florian Wurm, Martin Karplus, Immanuel F. Luescher

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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-2K(d)-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 2β (CDR2β). 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 CDR3α and CDR2β. We conclude that TCR expressing selective Vβ and CDR3α sequences form a binding domain between CDR3α and CDR2β that can accommodate nonpeptidic moieties conjugated at the C-terminal portion of peptides binding to major histocompatibility complex (MHC) encoded proteins.

Original languageEnglish
Pages (from-to)3622-3631
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number6
DOIs
Publication statusPublished - 05 Feb 1999

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