Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of MBP peptide that are important for T cell receptor recognition are prominent, solvent exposed residues in the crystal structure. A distinguishing feature of the HLA-DR2 peptide binding site is a large, primarily hydrophobic P4 pocket that accommodates a phenylalanine of the MBP peptide. The necessary space for this aromatic side chain is created by an alanine at the polymorphic DRβ 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases.
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19 October 1998
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October 19 1998
Crystal Structure of HLA-DR2 (DRA*0101, DRB1*1501) Complexed with a Peptide from Human Myelin Basic Protein
Kathrine J. Smith,
Kathrine J. Smith
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
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Jason Pyrdol,
Jason Pyrdol
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
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Laurent Gauthier,
Laurent Gauthier
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
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Don C. Wiley,
Don C. Wiley
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
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Kai W. Wucherpfennig
Kai W. Wucherpfennig
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
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Kathrine J. Smith
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
Jason Pyrdol
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
Laurent Gauthier
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
Don C. Wiley
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
Kai W. Wucherpfennig
From the *Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115; the ‡Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138; the §Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115; and the ‖Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115
Address correspondence to Kai W. Wucherpfennig, Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Phone: 617-632-3086; Fax: 617-632-2662; E-mail: [email protected]
We have benefited from the continuing collaboration with Dr. Jack L. Strominger on aspects of MHC biology. K.W. Wucherpfennig would like to thank Dr. Jack L. Strominger for encouragement and support during earlier stages of the project.
Coordinates will be deposited in the Protein Data Bank (Brookhaven National Laboratory, Upton, NY) and are available before their release by E-mail ([email protected]).
Received:
July 14 1998
Revision Received:
August 18 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (8): 1511–1520.
Article history
Received:
July 14 1998
Revision Received:
August 18 1998
Citation
Kathrine J. Smith, Jason Pyrdol, Laurent Gauthier, Don C. Wiley, Kai W. Wucherpfennig; Crystal Structure of HLA-DR2 (DRA*0101, DRB1*1501) Complexed with a Peptide from Human Myelin Basic Protein . J Exp Med 19 October 1998; 188 (8): 1511–1520. doi: https://doi.org/10.1084/jem.188.8.1511
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