1. Covalent HLA-B27/peptide complex induced by specific recognition of an aziridine mimic of arginine.
- Author
-
Weiss, GA, Valentekovich, RJ, Collins, EJ, Garboczi, DN, Lane, WS, Schreiber, SL, and Wiley, DC
- Subjects
Humans ,Aziridines ,Arginine ,Peptides ,HLA-B27 Antigen ,HLA-DR1 Antigen ,Affinity Labels ,Ligands ,Circular Dichroism ,Binding Sites ,Protein Binding ,Thermodynamics - 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.
- Published
- 1996