title: Predicting interactions between T cell receptors and MHC-peptide complexes.
abstract: Conserved interactions between T cell receptors (TCRs) and major histocompatibility complex (MHC) proteins with bound peptide antigens are not well understood. In order to gain a better understanding of the interaction modes of human TCR variable (V) regions, we have performed a structural analysis of the TCRs bound to their MHC-peptide ligands in human, using the available structural models determined by X-ray crystallography. We identified important differences to previous studies in which such interactions were evaluated. Based on the interactions found in the actual experimental structures we developed the first rule-based approach for predicting the ability of TCR residues in the complementarity-determining region (CDR) 1, CDR2, and CDR3 loops to interact with the MHC-peptide antigen complex. Two relatively simple algorithms show good performance under cross validation.
authors.affiliation: Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, 66123 Saarbruecken, Germany. roomp@mpi-inf.mpg.de
authors.forename: Kirsten
authors.initials: K
authors.lastname: Roomp
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Domingues
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen; D006649:Histocompatibility Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology*
chemical_list: D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D006649:Histocompatibility Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell