Biomaterial Database

Predicting affinity and specificity of antigenic peptide binding to major histocompatibility class I molecules. 2009

Florian Sieker, and Andreas May, and Martin Zacharias

School of Engineering and Science, Jacobs University Bremen, D-28759 Bremen, Germany.

Major Histo-Compatibility (MHC) class I molecules are major agents of the mammalian adaptive immune system. Class I molecules bind short antigenic peptides with a length of 8-10 residues in the Endoplasmatic Reticulum (ER) and after transport to the cell surface the peptides are presented to T-lymphocytes. The binding site of class I molecules is formed by a deep cleft between two alpha-helices at top of an extended beta-sheet. Only tightly bound high-affinity peptides have a chance to reach the cell surface and trigger an immune response. It is therefore of great interest to identify possible high-affinity antigenic peptides that could be used as vaccines to help the immune system to detect viral infections or kill malignant cells. A large number of crystal structures of antigenic peptides in complex with class I alleles have been determined that allow to understand the structural details important for peptide binding. Biophysical and biochemical analysis of peptide-class I complexes has resulted in a number of rules concerning the selection of high-affinity peptides. However, an accurate prediction of allele specific peptide-binding is still not possible. This issue is currently addressed by various computational tools developed by the bioinformatics community. The computational efforts range from statistical analysis of peptide motifs stored in databases to application of neural network methods and support vector machine approaches. In addition, structure based approaches to predict class I binding specificity including molecular modeling and molecular dynamics (MD) simulations will also be presented.

UI	MeSH Term	Description	Entries
D008390	Markov Chains	A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system.	Markov Process,Markov Chain,Chain, Markov,Chains, Markov,Markov Processes,Process, Markov,Processes, Markov
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000939	Epitopes	Sites on an antigen that interact with specific antibodies.	Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D015395	Histocompatibility Antigens Class I	Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.	Class I Antigen,Class I Antigens,Class I Histocompatibility Antigen,Class I MHC Protein,Class I Major Histocompatibility Antigen,MHC Class I Molecule,MHC-I Peptide,Class I Histocompatibility Antigens,Class I Human Antigens,Class I MHC Proteins,Class I Major Histocompatibility Antigens,Class I Major Histocompatibility Molecules,Human Class I Antigens,MHC Class I Molecules,MHC-I Molecules,MHC-I Peptides,Antigen, Class I,Antigens, Class I,I Antigen, Class,MHC I Molecules,MHC I Peptide,MHC I Peptides,Molecules, MHC-I,Peptide, MHC-I,Peptides, MHC-I
D016571	Neural Networks, Computer	A computer architecture, implementable in either hardware or software, modeled after biological neural networks. Like the biological system in which the processing capability is a result of the interconnection strengths between arrays of nonlinear processing nodes, computerized neural networks, often called perceptrons or multilayer connectionist models, consist of neuron-like units. A homogeneous group of units makes up a layer. These networks are good at pattern recognition. They are adaptive, performing tasks by example, and thus are better for decision-making than are linear learning machines or cluster analysis. They do not require explicit programming.	Computational Neural Networks,Connectionist Models,Models, Neural Network,Neural Network Models,Neural Networks (Computer),Perceptrons,Computational Neural Network,Computer Neural Network,Computer Neural Networks,Connectionist Model,Model, Connectionist,Model, Neural Network,Models, Connectionist,Network Model, Neural,Network Models, Neural,Network, Computational Neural,Network, Computer Neural,Network, Neural (Computer),Networks, Computational Neural,Networks, Computer Neural,Networks, Neural (Computer),Neural Network (Computer),Neural Network Model,Neural Network, Computational,Neural Network, Computer,Neural Networks, Computational,Perceptron