Identification of the cognate peptide-MHC target of T cell receptors using molecular modeling and force field scoring
| Autor: | Esteban Omar Lanzarotti, Paolo Marcatili, Morten Nielsen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular PIPELINE CIENCIAS MÉDICAS Y DE LA SALUD Molecular model T-Lymphocytes Immunology Receptors Antigen T-Cell Ciencias de la Salud Peptide chemical and pharmacologic phenomena T-Cell Antigen Receptor Specificity Computational biology Antigen-Antibody Complex Major histocompatibility complex Microscopy Atomic Force 01 natural sciences Epitope Force field (chemistry) Article T CELL RECEPTOR Major Histocompatibility Complex 03 medical and health sciences Epitopes Immune system 0103 physical sciences Humans Amino Acid Sequence Molecular Biology chemistry.chemical_classification 010304 chemical physics biology Chemistry Immunogenicity T-cell receptor MODELLING ANTIGENS/PEPTIDES/EPITOPES Otras Ciencias de la Salud 030104 developmental biology biology.protein MHC Peptides Protein Binding |
| Zdroj: | Lanzarotti, E, Marcatili, P & Nielsen, M 2018, ' Identification of the cognate peptide-MHC target of T cell receptors using molecular modeling and force field scoring ', Molecular Immunology, vol. 94, pp. 91-97 . https://doi.org/10.1016/j.molimm.2017.12.019 |
| Popis: | Interactions of T cell receptors (TCR) to peptides in complex with MHC (p:MHC) are key features that mediate cellular immune responses. While MHC binding is required for a peptide to be presented to T cells, not all MHC binders are immunogenic. The interaction of a TCR to the p:MHC complex holds a key, but currently poorly comprehended, component for our understanding of this variation in the immunogenicity of MHC binding peptides. Here, we demonstrate that identification of the cognate target of a TCR from a set of p:MHC complexes to a high degree is achievable using simple force-field energy terms. Building a benchmark of TCR:p:MHC complexes where epitopes and non-epitopes are modelled using state-of-the-art molecular modelling tools, scoring p:MHC to a given TCR using force-fields, optimized in a cross-validation setup to evaluate TCR inter atomic interactions involved with each p:MHC, we demonstrate that this approach can successfully be used to distinguish between epitopes and non-epitopes. A detailed analysis of the performance of this force-field-based approach demonstrate that its predictive performance depend on the ability to both accurately predict the binding of the peptide to the MHC and model the TCR:p:MHC complex structure. In summary, we conclude that it is possible to identify the TCR cognate target among different candidate peptides by using a force-field based model, and believe this works could lay the foundation for future work within prediction of TCR:p:MHC interactions. Fil: Lanzarotti, Esteban Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Marcatili, Paolo. Technical University of Denmark; Dinamarca Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; Dinamarca |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|