title: Genome-wide structural modelling of TCR-pMHC interactions.
abstract: BACKGROUND
  The adaptive immune response is antigen-specific and triggered by pathogen recognition through T cells. Although the interactions and mechanisms of TCR-peptide-MHC (TCR-pMHC) have been studied over three decades, the biological basis for these processes remains controversial. As an increasing number of high-throughput binding epitopes and available TCR-pMHC complex structures, a fast genome-wide structural modelling of TCR-pMHC interactions is an emergent task for understanding immune interactions and developing peptide vaccines.
  
  
  RESULTS
  We first constructed the PPI matrices and iMatrix, using 621 non-redundant PPI interfaces and 398 non-redundant antigen-antibody interfaces, respectively, for modelling the MHC-peptide and TCR-peptide interfaces, respectively. The iMatrix consists of four knowledge-based scoring matrices to evaluate the hydrogen bonds and van der Waals forces between sidechains or backbones, respectively. The predicted energies of iMatrix are high correlated (Pearson's correlation coefficient is 0.6) to 70 experimental free energies on antigen-antibody interfaces. To further investigate iMatrix and PPI matrices, we inferred the 701,897 potential peptide antigens with significant statistic from 389 pathogen genomes and modelled the TCR-pMHC interactions using available TCR-pMHC complex structures. These identified peptide antigens keep hydrogen-bond energies and consensus interactions and our TCR-pMHC models can provide detailed interacting models and crucial binding regions.
  
  
  CONCLUSIONS
  Experimental results demonstrate that our method can achieve high precision for predicting binding affinity and potential peptide antigens. We believe that iMatrix and our template-based method can be useful for the binding mechanisms of TCR-pMHC complexes and peptide vaccine designs.
authors.forename: I-Hsin
authors.initials: IH
authors.lastname: Liu
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Lo
authors.forename: Jinn-Moon
authors.initials: JM
authors.lastname: Yang
mesh_terms: D056704:Adaptive Immunity; D001665:Binding Sites; D015894:Genome, Human; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results; D012984:Software
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell