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Covalent HLA-B27/peptide complex induced by specific recognition of an aziridine mimic of arginine.

Authors
  • Weiss, G A
  • Valentekovich, R J
  • Collins, E J
  • Garboczi, D N
  • Lane, W S
  • Schreiber, S L
  • Wiley, D C
Type
Published Article
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publication Date
Oct 01, 1996
Volume
93
Issue
20
Pages
10945–10948
Identifiers
PMID: 8855288
Source
Medline
License
Unknown

Abstract

The class I major histocompatibility complex (MHC) glycoprotein HLA-B27 binds short peptides containing arginine at peptide position 2 (P2). The HLA-B27/peptide complex is recognized by T cells both as part of the development of the repertoire of T cells in the cellular immune system and during activation of cytotoxic T cells. Based on the three-dimensional structure of HLA-B27, we have synthesized a ligand with an aziridine-containing side chain designed to mimic arginine and to bind covalently in the arginine-specific P2 pocket of HLA-B27. Using tryptic digestion followed by mass spectrometry and amino acid sequencing, the aziridine-containing ligand is shown to alkylate specifically cysteine 67 of HLA-B27. Neither free cysteine in solution nor an exposed cysteine on a class II MHC molecule can be alkylated, showing that specific recognition between the anchor side-chain pocket of an MHC class I protein and the designed ligand (propinquity) is necessary to induce the selective covalent reaction with the MHC class I molecule.

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