Nature 368, 215 - 221 (17 March 1994); doi:10.1038/368215a0

Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide

Lawrence J. Stern^*, Jerry H. Brown^†, Theodore S. Jardetzky^*, Joan C. Gorga^‡, Robert G. Urban, Jack L. Strominger & Don C. Wiley^*§

Department of Biochemistry and Molecular Biology, and the ^* Howard Hughes Medical Institute, Harvard University, 7 Divinity Avenue,Cambridge, Massachusetts 02138, USA
^† Rosenstiel Research Center, Brandeis University, 415 South Street, Waltham, Massachusetts 02254, USA
^‡ Rangos Research Center, Children's Hospital of Pittsburgh and University of Pittsburgh Medical Center, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA
^§ To whom correspondence should be addressed.

An influenza virus peptide binds to HLA-DR1 in an extended conformation with a pronounced twist. Thirty-five per cent of the peptide surface is accessible to solvent and potentially available for interaction with the antigen receptor on T cells. Pockets in the peptide-binding site accommodate five of the thirteen side chains of the bound peptide, and explain the peptide specificity of HLA-DR1. Twelve hydrogen bonds between conserved HLA-DR1 residues and the main chain of the peptide provide a universal mode of peptide binding, distinct from the strategy used by class I histocompatibility proteins.

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