Smith K J, Pyrdol J, Gauthier L, Wiley D C, Wucherpfennig K W
Department of Molecular Medicine, Children's Hospital, Boston, Massachusetts 02115, USA.
J Exp Med. 1998 Oct 19;188(8):1511-20. doi: 10.1084/jem.188.8.1511.
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 DRbeta 71 position. These features make the P4 pocket of HLA-DR2 distinct from DR molecules associated with other autoimmune diseases.
多发性硬化症的易感性与人类组织相容性白细胞抗原（HLA）-DR2（DRB1*1501）单倍型相关。HLA-DR2的结构是通过与人类髓鞘碱性蛋白（MBP）的结合肽确定的，该肽对人类MBP特异性T细胞具有免疫显性。MBP肽中对T细胞受体识别重要的残基在晶体结构中是突出的、暴露于溶剂中的残基。HLA-DR2肽结合位点的一个显著特征是一个大的、主要为疏水性的P4口袋，可容纳MBP肽的苯丙氨酸。该芳香侧链所需的空间由多态性DRβ71位置的丙氨酸形成。这些特征使HLA-DR2的P4口袋不同于与其他自身免疫性疾病相关的DR分子。
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