structural properties of mhc class ii ligands, implications for the prediction of mhc class ii epitopesmhc ii类配体的结构特性,对mhc ii类抗原表位的预测的影响.pdfVIP

Structural Properties of MHC Class II Ligands, Implications for the Prediction of MHC Class II Epitopes 1 2 1 Kasper Winther Jørgensen , Søren Buus , Morten Nielsen * 1 Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark, 2 Laboratory of Experimental Immunology, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark Abstract Major Histocompatibility class II (MHC-II) molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule, allowing binding of peptides extending out of the binding groove. Furthermore, only a few HLA-DR alleles have been characterized with a sufficient number of peptides (100–200 peptides per allele) to derive accurate description of their binding motif. Little work has been performed characterizing structural properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC class II ligands by integrating prediction of MHC- peptide binding with prediction of surface exposure and protein secondary structure. This combined pre