Structural Basis for the Presentation of Tumor Associated MHC Class II Restricted Phosphopeptides to CD4+ T Cells英文电子书.pdfVIP

doi:10.1016/j.jmb.2010.04.037 J. Mol. Biol. (2010) 399, 596–603 Available online at Structural Basis for the Presentation of Tumor-Associated MHC Class II-Restricted Phosphopeptides to CD4+ T Cells Yili Li 1,2†, Florence R. Depontieu3 †, John Sidney4 , Theresa M. Salay3 , Victor H. Engelhard5 , Donald F. Hunt6,7 , Alessandro Sette4 , Suzanne L. Topalian3 ⁎ and Roy A. Mariuzza 1,2⁎ 1University of Maryland Institute Dysregulated protein phosphorylation is a hallmark of malignant transfor- for Bioscience and Biotechnology mation. Transformation can generate major histocompatibility complex Research, W. M. Keck Laboratory (MHC)-bound phosphopeptides that are differentially displayed on tumor for Structural Biology, Rockville, cells for specific recognition by T cells. To understand how phosphorylation MD 20850, USA alters the antigenic identity of self-peptides and how MHC class II 2 molecules present phosphopeptides for CD4+ T-cell recognition, we Department of Cell Biology and determined the crystal structure of a phosphopeptide derived from Molecular Genetics, University of melanoma antigen recognized by T cells-1 (pMART-1), selectively Maryland, College Park, expressed by human melanomas, in complex with HLA-DR1. The structure MD 20742, USA revealed that the phosphate moiety attached to the serine residue at position 3Department of Surgery and the P5 of pMART-1 is available for direct interactions with T-cell receptor (TCR) Sidney Kimmel Comprehensive and that the peptide N-terminus adopts an unusual conformatio