MULTIPRED: a computational system for prediction of promiscuous HLA binding peptides

MULTIPRED is a web-based computational system for the prediction of peptide binding to multiple molecules (proteins) belonging to human leukocyte antigens (HLA) class I A2, A3 and class II DR supertypes. It uses hidden Markov models and artificial neural network methods as predictive engines. A novel data representation method enables MULTIPRED to predict peptides that promiscuously bind multiple HLA alleles within one HLA supertype. Extensive testing was performed for validation of the prediction models. Testing results show that MULTIPRED is both sensitive and specific and it has good predictive ability (area under the receiver operating characteristic curve AROC > 0.80). MULTIPRED can be used for the mapping of promiscuous T-cell epitopes as well as the regions of high concentration of these targets—termed T-cell epitope hotspots. MULTIPRED is available at .

[1]  Steven G.E. Marsh,et al.  Nomenclature for factors of the HLA system, update , 2007 .

[2]  Vladimir Brusic,et al.  Neural Models for Predicting Viral Vaccine Targets , 2005, J. Bioinform. Comput. Biol..

[3]  J. Hammer,et al.  Discovery of promiscuous HLA-II-restricted T cell epitopes with TEPITOPE. , 2004, Methods.

[4]  Vladimir Brusic,et al.  Computational methods for prediction of T-cell epitopes--a framework for modelling, testing, and applications. , 2004, Methods.

[5]  Vladimir Brusic,et al.  Prediction of class I T-cell epitopes: evidence of presence of immunological hot spots inside antigens , 2004, ISMB/ECCB.

[6]  O. Lund,et al.  Definition of supertypes for HLA molecules using clustering of specificity matrices , 2004, Immunogenetics.

[7]  H. Ploegh,et al.  Class II MHC peptide loading by the professionals. , 2004, Current opinion in immunology.

[8]  S. Marsh Nomenclature for factors of the HLA system, update September 2003. , 2003, Tissue antigens.

[9]  Channa K. Hattotuwagama,et al.  Quantitative online prediction of peptide binding to the major histocompatibility complex. , 2004, Journal of molecular graphics & modelling.

[10]  Ellis L Reinherz,et al.  Genome-wide Characterization of a Viral Cytotoxic T Lymphocyte Epitope Repertoire* , 2003, Journal of Biological Chemistry.

[11]  S Brunak,et al.  Sensitive quantitative predictions of peptide-MHC binding by a 'Query by Committee' artificial neural network approach. , 2003, Tissue antigens.

[12]  John Sidney,et al.  Examining the independent binding assumption for binding of peptide epitopes to MHC-I molecules , 2003, Bioinform..

[13]  Arne Elofsson,et al.  Prediction of MHC class I binding peptides, using SVMHC , 2002, BMC Bioinformatics.

[14]  E. Reinherz,et al.  Prediction of MHC class I binding peptides using profile motifs. , 2002, Human immunology.

[15]  Vladimir Brusic,et al.  Prediction of promiscuous peptides that bind HLA class I molecules , 2002, Immunology and cell biology.

[16]  J. Yewdell,et al.  Cut and trim: generating MHC class I peptide ligands. , 2001, Current opinion in immunology.

[17]  J. Deussing,et al.  Proteases involved in MHC dass II antigen presentation , 1999, Immunological reviews.

[18]  J. Sidney,et al.  Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism , 1999, Immunogenetics.

[19]  H. Rammensee,et al.  SYFPEITHI: database for MHC ligands and peptide motifs , 1999, Immunogenetics.

[20]  P. Cresswell,et al.  Mechanisms of MHC class I--restricted antigen processing. , 1998, Annual review of immunology.

[21]  L C Harrison,et al.  MHCPEP: a database of MHC-binding peptides. , 1994, Nucleic acids research.

[22]  A Sette,et al.  Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. , 1994, Journal of immunology.

[23]  Don C. Wiley,et al.  Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide , 1994, Nature.

[24]  K. Parker,et al.  Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. , 1994, Journal of immunology.

[25]  H. Rammensee,et al.  Peptides naturally presented by MHC class I molecules. , 1993, Annual review of immunology.

[26]  M. Torres,et al.  Nomenclature for factors of the HLA system. , 2011, Bulletin of the World Health Organization.