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. 1996 Oct 1;93(20):10945–10948. doi: 10.1073/pnas.93.20.10945

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

G A Weiss 1, R J Valentekovich 1, E J Collins 1, D N Garboczi 1, W S Lane 1, S L Schreiber 1, D C Wiley 1
PMCID: PMC38263  PMID: 8855288

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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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